Lessons learned

by Pheziwe Mshunqwane

This year has been one of the most challenging years yet the most fulfilling year. I have laughed until my stomach hurt; I have cried until there were no tears coming out. I have also prayed like I have never prayed before.

This year has taught me two most valuable lessons that I will always carry with me and these lessons are:

(a) ‘No man is an island’

I always thought that success depends on me and I can do it all on my own, but this year has taught the power of community. I have been blessed with the most supportive bunch of people; my fellow mates, supervisors and every one in my lab. I can confidently say, without then I would have probably given up.

(b) ‘Closed mouths never get fed’

I was this year that I learned to open my mouth and say ‘I’m not okay’, ‘I need help’ and it was then that I was able to get help and find the support that I needed. This was one of the hardest things for me to do but the environment that my group created has allowed me to break out of that cocoon.

I am grateful that I got to learn these lessons this year. I will take wherever I go.

You need to be comfortable with being uncomfortable in order to see growth. Read that again and slowly.

by Limpho Thipane

This year was a journey I was not ready for! From when I arrived in Cape Town, I struggled with accommodation, and I kept telling myself that I majored in Psychology, so I know how to counsel myself and deal with it. However, there is a famous saying “a doctor, cannot heal thyself” so the Psychology I learnt did not help. Bear in mind, I am far from home with no accommodation and funding. There were 2 voices, the first one told me to go back home because this is too much handle and the other one that I chose to listen to, said I should stay, and I will get through this and within days it was sorted. After that, another struggle or weight on my shoulders was funding. After weeks of stress, it got sorted out. Now another struggle was the transition from NWU to UCT and going back to contact lessons. We might have studied the same work in undergrad, but the content was totally different. In between my struggles of accommodation and funding, we had classes too. In my entire schooling years, I have never struggled academically the way I did this year! It came as a shock and even now I still ask myself what went wrong or what did I do wrong, because the frustration stemmed from putting in the hours, but they seem like they were not enough. Again, another struggle I faced was losing a loved one during all of that. Doing neurosciences and physiology came as a blessing and it is something I do not take for granted, because I managed to help my relative while he was having a stroke over the phone. Even on his funeral, I was unable to go because I had class, so I had to show up and exams were close. Basically, the most written word here is STRUGGLE and no matter what happened, I told myself that I should just take it 1 day at a time and it shall pass. Now my honours project, which challenged me to be uncomfortable because I had no background in immunology but the day I started, I told myself that I came here to learn and that is what I did. From doing lab work until late hours, my samples getting contaminated week after week, using chemistry calculations I did in Garde 10 which felt like decades ago and working with MICE! I know, you would expect me to be scared, but I wasn’t like which surprised my supervisors, like I said my project challenged me and I was grateful. But I’m probably going to scream when I see a mouse on the street! One thing that got me through this year was the support system I had, which I will always be grateful for! This year, I learnt a lot about myself and as much as I went through a lot in a short period of time, I am filled with gratitude and I learnt that life or growing up is not swift, easy or gradual, but it is a bumpy road, and it works out in the end. The months became weeks, weeks became days, and I am typing this after being finished with my academic year. So push, it will be worth it at the end. As the journey continues….

Honours- Don’t knock it till you try it.

by Casey Valentine

As the year draws to the end and there are only final presentations left to go, I find it is the perfect time to really reflect on how this past academic year has treated me and what I have learned from it. Before starting the year, I was filled with excitement. I was coming to a new university after achieving my undergraduate degree from the University of the Western Cape. When the course finally started, it began with a general course with all the Honours students (studying different degrees), and I felt quite lost. I didn’t know how this university functioned and what was really expected. It was quite unsettling at first which made me feel quite worried as I didn’t want to fall behind and have my first year of postgraduate studies not go well. However, once we were settled into our separate little groups of different divisions and faculties, I could be excited again. Since lockdown took over the past two years, I had limited lab experience when starting however I didn’t need to worry as everyone around, including supervisors or lab managers were so supportive and helpful, it really gave me the reassurance I needed. That support made me feel like I was doing the right thing and I was in the right place. The different modules were so interesting, and it opens your eyes to different options within your field in case you’re worried about where to go next. Without a doubt Honours was a challenging year and there were many long nights and early mornings and -make sure to stay hydrated, because there will be many tears. However, I would do it all again. Of course, it is a honour to be able to continue your studies and not many get the chance, but I feel the best past of this year has been the people that I have encountered. From my phenomenal honours class to my supervisor, HOD and of course my family. Everyone has helped to build me up. When you feel like you’re at your lowest point and doubt being able to finish the year and doubt your abilities. All the encouragement and support gives you a fight to continue. You develop such a deep and strong relationship with everyone around you that I would advise anyone to do Honours just to experience this relationship. It is worth every tear to be here. I trust that everything happens for a reason and God has set out a plan for us that we are unaware of. I am so grateful that this was part of His plan for me.

Where do I even begin? 

by Yanelisa Pulani

Perhaps I should begin by saying that this year has been a serious rollercoaster ride – fun, scary, stretching, yet rewarding. 

My path to becoming a clinician scientist began only a year ago. Or perhaps I’m lying. Perhaps the journey began in 2013 and 2014, and most recently in 2018. In 2013, and 2014, I lost my aunt and nana to pancreatic and oesophageal cancer, respectively. Between the early years and 2018, we discovered that my uncle has schizophrenia, and in 2018, my sister was diagnosed with epilepsy, the cause of which is still unknown. These experiences motivated me to seek solutions for which a medical degree alone would not have allowed me to search to the best of my abilities, and thus the integration of science and medicine made perfect sense and gave me hope for the future of health care. And the confirmation I received in 2019 to begin research in neurosciences or genetics was the final nail in the coffin for me to take the first steps on this less-travelled path that serves as a pillar for the future. 

Last year, I took the first step into my journey by pursuing my third year of medicine with molecular medicine and, in the end, being accepted into the Neuroscience and Physiology stream, and my second step toward becoming a clinician scientist began. I joined UCT’s best lab, the Raimondo lab (this is scientifically proven, so don’t come after me). Officially, I am a member of the Raimondo lab, and unofficially, a member of the Crypto team, which is led by Dr. Dangarembizi, the greatest female neuroscientist of all time if you ask me. I couldn’t have made it through the year without the help of these two groups. But I have to give special credit to my supervisor, Joe; I couldn’t have asked for a better supervisor. I’ve never met anyone so humble and caring. He prioritized my mental health, and coming from Medicine, where mental health is often treated as a foreign language and pushed to the side, I appreciated being seen and treated as a “feeling” human being for once. If you need a lab that will push you to do your best in a less-stressful way, this is the lab to be in (if you’re doing Neuro). Thesis writing almost caused me to quit, but the encouragement I received from my team, Joe, Thijs (who was always up with me in the early AMs), and Roxanne, was so compelling that I had to get up. 

Friends were never on my list of things I expected to walk out with this year. I am extremely grateful for the friendships (the 2022 Neuro crew) I have made. We’ve made so many wonderful memories together, from First Thursdays to Saturday food markets, color picnics, pizza, and games night. We connected, in part because of our extremely weird personalities, and I loved every minute of it. I could not have done honors with a better group of people. I’m looking forward to seeing what these wonderful people accomplish in their careers. 

My second step toward becoming a clinician scientist was fantastic! I have gained many valuable skills that I will carry with me on my next journey of intercalated Master’s. 

If you know me, you know that I can’t end a reflection piece without mentioning God. It may appear inappropriate to many, but until you know my life and how God has shown up in the darkest of times, this will appear useless to you, but I guess I don’t really care. The right ears will hear this and that’s all that matters.   That being said, I am most grateful for the way God always shows up in my life. From instilling in me the desire to conduct brain research to paving the way for me through the intercalated program and now my honors degree. He is far superior at aligning my needs with His plan for me. This year could have been much worse, but His plan was far greater, and He carried the rope and brought people into my life to help me get through this season seamlessly. 

pov: I am dating my project…

by Sethu Poswa

It was Valentine’s day when we first met, and I remember being excited to have been introduced to them. As soon as we had met, I did not expect to move as fast as we did. I found myself spending more time with them, finding out more about them and gaining a deeper understanding of what they are about as our weeks together progressed. The more time I spent with them, the more I found myself pondering them, whether I was at church, during my lunch breaks or while I was going out for an afternoon stroll. I even found myself dreaming about them at times.

As much as I enjoyed our time together, I will still be petty enough to bring up the fact that it was a love-hate relatiuonship in that I loved them but they hated me. Slowly but surely, “Where have you been?” was the new “Hello” when answering a phone call from friends and relatives and I had wondered when I had started placing so much emphasis on ensuring that they had my undivided attention for 24 hours of the day. Perhaps it was during all those late nights spent together at the lab or perhaps it was when I would turn down at least 95% of my weekend plans just because I was not sure whether they would approve of me spending time with anyone else. Of course, it did not help that I was always spoke of being with them if I wasn’t in their presence. One could have called me obsess-I mean infatuated at this moment in time.

Oddly enough, the saddest part of this relationship was the break-up. Yes, the break-up. This relationship was coming to an end, and we could both feel it. The only way I know how to describe that feeling is to describe it as something that felt as though it was coming to completion. Nowadays I still find myself yearning for just a little bit more time with them, even if that means there is a chance that I might pull out my hair out of frustration.

With all that is said and done, this was a very enjoyable relationship that helped me realise what I am capable of. Never have I ever been pushed so hard by anyone or anything in my life, and the fact that I was able to make it has taught me a lot about myself. In the distant future I am hoping to meet with other projects along the way, who knows maybe the next project might lead to a proposal…A project proposal, that is, for master’s….

Your happiness lies in your own hands

by Jeanice Rose Bourobou Boukamba

I am tempted to write that 2021 was not so bad, but after deep reflection I will say it was great!

It’s the year when I finally managed to free myself from my bad anxiety and panic attacks. It started on a good note, I made some awesome resolution, after three years of isolation, I finally decided to boost my social life and start connecting with people. In 2021 I decided to just let myself “be”, and I learn how to balance my student life with the rest.

2021 was the only year I felt a profound disappointment; I received reject letters from most of the Universities I applied to. After four years of hard work, the letters I was receiving made me feel like I wasn’t good enough. It was with sadness that I was thinking that my efforts where meaningless.  I was seeing my dream of becoming a medical researcher flying away until I received an acceptance letter from UCT.

The bitter taste I had from the eight letters I received before my admission prevented me from savoring my achievement. I regret this moment. With hindsight, I understood that I can’t always have everything I want therefore I decided that in 2022:

I must always be happy and celebrate my achievements. This attitude will keep me motivated and productive.

I should stop focusing on what I did not get but rather on what I have or can get from my hard work. One needs to go through the falling down to learn how to walk.

To end my short reflection, I will say that positivity is the key to happiness and success, at the end of the day we become what we think we are.

The Importance of Contemplation in The Journey of Life

by Siphamandla Ngwenya

I’ve always found it hard to express my thoughts, be it in writing or properly articulating what I’m thinking. As hard as my honour’s year has been, I have to say it has been one of the greatest experiences I’ve had in my life because it has allowed to me to grow as an individual. One of the major practices that has given me the mental capacity to surpass my limits this year is contemplating about all the things that have happened to get me to where I am today, and what the future holds for me based on the choices I make.

I would define contemplation as the act of continuously pondering over a question in the mind without bias to investigate the nature, the truth, or the very essence of the thing in question. Contemplation techniques in my eyes are a fundamental requirement of any individual who aims to improve their way of living, emotional intelligence, learning abilities and overall, their mental well-being.

When I was younger, there was a moment when I wondered how I was breathing and I had a brief panic phase because of the series of questions I asked myself – “How am I breathing?”, “How am I thinking?”, “Why am I me?”, “Am I inhabiting the brain?”, or “Am I the brain?”. Children are naturally curious but when we grow, our curiosity is drained out and these reflective questions broadened my horizon and re-ignited my curiosity to all my surroundings. Indeed, there is so much to unearth from the path taken by a curious mind.

The state of the school system these days rewards standardization and adherence to rules, rather than rewarding exploration, which has led to a lot of students losing curiosity. I am fortunate enough in the sense that when I look back at the schools I studied in – from primary school to the tertiary institution, they played a significant role in preserving my curiosity. Over time, my imagination and curiosity expanded and at present, I’m in the field of infectious diseases and immunology, because I’m overly curious of how the body interacts with microorganisms and how it influences the onset of diseases.

Through my honours journey, what I’ve found particularly interesting is the relationship between contemplative practises and critical thinking. As scientists to be, it is crucial that we improve our critical thinking. Contemplation plays a crucial role in this because science itself is an art of deep thought based on questions that keep us awake at night and conducting experiments to answer those burning questions. In essence, the best scientific innovations were born out of great minds, who were not confined to a narrow thought process.

Contemplation especially this year has been a cornerstone in creating meaning to my life in a world that is pointless, but at the same time not pointless. I find comfort in that because I know that I can create my own meaning of life, while other people may feel an empty void. Considering this, I would challenge the latter to put down their expectations of what the world should be and unlearn the negative assumptions of meaninglessness. I ask you to take a moment and reflect on this – If you do see your life as not having a purpose, exit that mind space, contemplate, and try to see your life’s worth as part of a puzzle that would be incomplete without you.

Trust your gut.

by Micaela Louise Swart

At the end of last year, upon the completion of my undergraduate degree, I was faced with an incredibly difficult decision. The decision was whether to pursue my honours degree in Medical Microbiology, or in Biomedical Forensic Science.

You see, I had majored in Medical Microbiology during my undergrad and was actually pretty good at it, so that was a comfortable option for me. The thought of studying Medical Microbiology however did not excite me like Forensics did. I guess I have the same reason for wanting to study forensic science as most other students – because of CSI and those other intriguing true crime documentaries. My boyfriend never understood my love for those shows. My longing to study forensic science went deeper than that though. I wanted to contribute to the medico-legal system of South Africa. I wanted to seek justice for families, and help them find some level of closure. I wanted to be part of something greater.

I made an effort to speak to individuals from the SAPS Forensic Laboratories to obtain any valuable advice or information about the forensics field. They warned me about the lack of resources and other issues experienced in their labs, as well as the lack of growth opportunities at SAPS specifically. Some even tried to steer me away from forensics as a career choice because of their negative experiences. This made me doubt whether forensic science was the route for me to pursue.

I spoke to my family and friends about the decision that had to be made, and asked for their thoughts and guidance. Hearing their perspectives was so incredibly helpful, as they are all in the working world. They expressed that my voice and body language changed when speaking about forensics, like something lit up inside of me. They knew that forensics was the path for me, and deep down, I knew it too. I guess the difficulty rested in whether I wanted to pick the safe, comfortable option, or the one that I was truly passionate about, but came with more uncertainties. After much debate with those in my life, going backwards and forwards with myself, as well as writing pros-and-cons lists, I decided to trust my gut.  I decided to choose something that I was going to look forward to studying every day, even if I didn’t know what the future held for that particular field.

Now, looking back, I realise that Medical Microbiology has not once crossed my mind since my first day of honours in Biomedical Forensic Science. This year has been life changing. I’ve been privileged enough to be supervised by one of the most knowledgeable individuals I’ve ever come across; I’ve formed some of the healthiest friendships I’ve ever had; I’ve been shown patience, encouragement, love and understanding by my small but incredibly supportive department. Truth is, I’ve enjoyed this year so much that I’ve decided to pursue my MSc in Biomedical Forensic Science. I guess you could say my gut was right.

Discovering my limits

by Darshni Naiker

I completed my undergrad in the University of Kwa-Zulu Natal in Medical science: Anatomy, thereafter I moved to Cape Town, where I got the opportunity to study in the University of Cape Town doing forensic science and as much as this as always been a goal of mine the difference in level of work load was evident from day one. However, during the course of the first semester, I learnt so many new and intriguing concepts of forensic science including performing different analyses, scientific writing, and professionalisms. There was times when things would get overwhelming but being exposed to new ideas and concepts I have not been introduced to in undergrad pushed me to work harder and challenge myself. I learnt to questions issues or situations and try to apply the theory taught into assignments given and problems I faced.

Even though I did have to work on a project in undergrad, the experience is entirely different. I have gained a lot of knowledge of a field I previously had no interest in. Every component of the project has helped me grow as an individual and scientist. The research done for my project helped me understand the value of reading articles and even though I sometimes still find interpreting articles difficult, reading many articles and talking to other students in the field as only further sparked my interest in entomology. A large component of my project has been lab work, and this allowed my to gain skills I did not have a chance too. Performing them for my project has not been without challenges and there are times when I get disappointed when experiments fail but I have learnt to accepts the outcomes, figure out what went wrong and work harder on the next one.

Another important part of the course that has left an impact on me is the presentations that was required of me to be done as assessments or for journal clubs. As someone who is afraid of public speaking this aspects was nerve wrecking and caused me a lot of anxiety but after completing a few the experience helped me be more prepared and get used to the idea of talking in front of people. This was an important skill to gain and helped me develop as a student and scientist. Throughout this roller-coaster of a year, I also gained some of the most supportive, encouraging, and inspiring friends. Despite their crazy busy schedules, they always seemed to make time to check in on me and sharing our daily troubles made each day better. All the situations, good and bad I have experienced so far has been so instrumental to me and my journey in University, I have discovered my limits and that I can handle more than I thought I was capable off. 


by Sanele Mdletshe

The liver is the most important organ of the body, it performs crucial metabolic functions, and these includes metabolizing toxic substances, producing bile for digestion and maintaining blood sugar levels. It is a very unique organ that is able to repair itself after damage, but this is not the case if the injury has progressed to cirrhosis, which is a chronic liver damage as a results of alcohol abuse or hepatitis. The ultimate treatment for end-stage cirrhosis is liver transplantation, but the shortage of donors remains a major obstacle. According to the global observatory on donation and transplantation, in 2020, the liver was the second most transplanted organ to save people’s lives. GLOBACAN estimates indicate that chronic liver diseases and liver cirrhosis contribute to more than 1 million deaths annually across the world.

In this study, researchers looked at the alternative options for treatment of chronic liver diseases and liver failure. The study was conducted based on the application of the principles of regenerative medicine and tissue engineering. Briefly, the aim was to use induced pluripotent stem cells (iPSCs) to enhance the repair of the liver after cirrhosis, this is due to their pluripotent properties which allows them to differentiate into all cell types including liver cells. iPSCs were generated by transfecting somatic fibroblasts with four transcription factors (OCT4, SOX2, KLF4 and MYC) famously known as “Yamanaka factors”.



Conclusion/take homes
In this study, authors established a three-step protocol to generate iPSC-derived hepatocytes that can be an alternative treatment for chronic liver diseases and liver failure, as assessed in mice with lethal fulminant hepatic failure. This protocol is very rapid and efficient as it takes only 12 days.

The use of iPSCs holds a great promise in medicine, its advantages includes overcoming ethics against the use of human embryonic stem cells, reduces the risk of immunosuppression as these cells are generated from the patient’s somatic cells.

Chen, Y., Tseng, C., Wang, H., Kuo,H., Yang, V.W., and Lee O.K. 2012. Rapid generation of mature hepatocyte-like cellsfrom human induced pluripotent stem cells by an efficient threestep protocol.

Taking a step back

by Katelyn Kalil

The undergrad experience is no doubt a stressful one. There are always numerous assignments that need submitting, tests every other week and practicals that seem to last entire evenings. The combination of this stress with the drop in marks from high school that the majority of us experience, also frequently leads to impostor syndrome. It is no wonder that by the time these three years are finished, many of us send off our applications for honours, take a vacation, and put it to the back of our minds.

I think that this lack of time to ourselves can often be detrimental. Paradoxically, we lose touch with our subjects and how we feel about them because we spend too much time fully engaged with them. My undergrad seemed to fly by. I enjoyed it and loved my majors, but I felt a little confused about where my future would take me or even what options were available.

COVID-19 came about during my 3rd and final year of my BSc undergrad which lead to me moving back home. It quickly became a year that lacked any form of routine, this was very detrimental to my studies at first. There seemed to be nothing but an abundance of time and I could not seem to spend it correctly no matter how many schedules I drew up. Luckily, I got a bit more of a grip on things in the second half of the year and my marks began to improve.

I also began to reconnect with some of my work again. Having some time to assess how you feel about the work you are doing is incredibly important. Undergrads are relatively broad and so when we pick what we want to specialise in it is helpful to have a good idea of the type of work we enjoy and the type of work we are good at and identify any overlaps.

I believe that the second half of the year helped me to do just that and I began to cross-check all of my work against my strengths and likes. Having time to do some of the things I enjoyed again was also incredibly helpful. It is important to not lose ourselves to work but rather to bring our best selves to the table- and that means living an all-rounded life, in whatever way that means to us as individuals.

After my plans of studies fell through due to air travel restrictions and applying for UCT honours and not getting in for the following year, I decided to take a gap year. During this gap year, I worked and completed online courses which have made this current year, doing honours, much easier.

I am aware that I was incredibly lucky with my COVID-19 experience. I had a supportive family and all the resources I needed. While, like most people, it also took its toll on my mental health, it also served as an opportunity to take a breather and reconnect with myself and my work. Although I still lack a clear plan for my future I am confident I am doing what I enjoy and for now, that is enough.

TB, is there anything we can do?

by Harry Kim

Mycobacterium Tuberculosis was first discovered in 1882 and it is still the leading cause of death of a single infectious agent. In 2019 alone, TB accounted for 10 million diagnosed cases and 1 to 2 million deaths. So the question arises, is there anything we can do?

The complexity of TB comes from the different levels of drug resistance the bacteria have. There are over 20 anti-TB drugs being used, all with varying resistance in the community. Undertreating leads to higher mortality and overtreating result in more significant side effects (often detrimental to patient’s life). So why after 140 years are we still making this mistake?

Due to the vast number of drugs, it is costly to have resistance testing facilitates for all anti-TB drugs. Often high TB burden countries are also developing countries and can only accommodate for isoniazid and rifampicin testing. So how do test more accurately?

All these problems have one answer: whole genome sequencing.

High throughput can be very expensive. However, in areas where TB is the number one cause of death, it can become an investment to improve the lives of the whole community as correct treatment can decrease mortality rates, decrease spread and improve symptom control.

The research shows 22% of local testing was incorrect according to the WGS testing, with half of these cases being inappropriately treated. It was also shown that 28% of mortalities had incorrect resistance testing. The odd ratio showed that patients are 4 times as likely to die when undertreated instead of receiving appropriate treatment.

The undertreatment of TB due to incorrect resistance testing results seems to be main culprit in this complex disease but whole genome sequencing is the answer to save millions.


Zürcher K, Reichmuth ML, Balif M, Louiseu C, Borrell S, Reinhard M, et al. Moratlity from drug-resistant tuberculosis in high-burden countries comparing routine drug susceptibility testing with whole-genome sequencing: a multicentre cohort study. Lancet. 2021 July;2:320-9.


by Petra Makua

The journey of moving to Cape Town from another province and another university happened so quickly. I don’t think it has sunk in yet that I’m a postgraduate student at UCT. I never saw myself changing universities to pursue a career in neuroscience. Honestly, I think I spent the first half of this year questioning my purpose and career path.

I could be getting ahead of myself here. Let’s start from the beginning.

Initially, I was excited to be studying a course related to the brain. I went into this thinking I would be pursuing a career in the clinical field, the practical stuff. Little did I know that postgraduate studies required so much reading! For someone who usually works alone, it meant I had to start engaging and communicating with people. To me, that felt like a nightmare. I must emphasize this once more; everything happened so fast! While trying to process this rude awakening, I also had to adapt to the new institution, make new friends, and always remember to carry a jacket with me even when it’s sunny outside because experiencing all four seasons in a day is normal in Cape Town.

I’m someone who prefers comfort and avoids stress, but in retrospect, this situation forced me to step out of my comfort zone. Through networking, I’ve met wonderful people who keep me motivated and are always teaching me new things. Moreover, I started attending workshops that have forced me to speak in public, and that alone has honed me as an individual. Reading journals provides so much satisfaction since you are constantly learning new things! I have also found a sense of comfort in doing lab work; I call it my “safe space.” Perhaps academia isn’t that bad after all.

Through all of this, I realised that sometimes all you need is a little push beyond your sanctuary for you to unleash your potential and grow as a person.

More Than What Meets an Eye

by Siphenathi Ntoba

Everyone is subject to challenging situations but those who trust in Almighty always rise like an edifice above them. This is how I live, and all life is spiritual and a mystery, but it is responsible for everyone to discover purpose in this life and walk worthy of it. This reflection communicates gratitude and positive mindset during troubling situations
experienced this year.

The best thing to do when you are face with diverse temptation find right people to talk to. As a student be able to talk one of your supervisors or else discern which supervisor can deal with your situation. Registration for 2022 academic year was an initial problem which happened for a month. This required me to constantly communicate with administration people through email from one person to another, and then I got academically registered. Finances were the biggest challenge, and that has contributed to my academic performance. However, during the month of June everything was in accordance with the Lord revealed that to me that time through His foreknowledge. I was so happy to see things fall into places irrespective of how my year began at UCT. This made my transitional period from undergraduate to honors program to be quite interesting and testing of character.

It was a pleasant experience to be in the laboratory (Lab) for me this year after COVID19 lockdown suffered me not a chance to be involved partially my undergraduate lab work and indeed this was amazing experience. This was really challenging at some point, but I finally won. The Lab manager was a nice and patient with each one of us, this re-assured us to be right student at the right place and well cared for. This kind of an atmosphere made it easy for us student propelled us for excellence regardless of lab challenges. Supervisors were amazing people who were always eager to assisting me in every way possible. I am grateful.

Trying to see clearly

by Casey Valentine

Macular dystrophies (MDs) are acknowledged as inherited retinal disorders which cause loss of vision due to the macula’s deterioration (1). Macular dystrophies cause irregularities that damage the macula and therefore affect the central vision (1). A common form of macular dystrophy is Stargardt disease which results from a mutation in the ABCA4 protein and is autosomal recessive. (2).

ABCA4 is the ATP-binding cassette transporter gene and is crucial for transporting vitamin A derivatives out of the visual cycle. Too much vitamin A will cause a toxic build-up and damage to the eye which resultsin blindness. ABCA4 is recognised as the most common cause of retinal degeneration in Mendelian inheritance.

A study performed by A. Auricchio et al. entitled “Gene Therapy of ABCA4-Associated Diseases” aimed to reveal the best treatment options for those affected by ABCA4-associated diseases (3). The study revealed that direct gene replacement therapy was the most promising treatment option as all ABCA-4 associated diseases are autosomal recessive and therefore the addition of a functional gene would re-establish visual function.

The main strategies considered for the transport of the genetic material included viral vectors and non-viral vectors. As the ABCA4 gene has a large sequence of 6.8kb, there was a challenge in finding the most appropriate vector as it would require a transport vector that has a large cargo capacity and effective photoreceptor (PR) capability (3).

The best nonviral strategy described included a polylysine-based compacted DNA nanoparticle (NP) CK30-NP, which showed improved effectiveness in ocular gene transfer. This method is beneficial as it allows the vector to enter the nucleus of cells and has the capacity for plasmids up to 20kb’s in length. (3) Moreover, a test performed on a homozygous null mutation of ABCA4 in a mouse model of Stargardt disease, indicated that 8 months after an injection of CK30-NP, there was improved recovery of dark adaptation and reduced lipofusion accumulation (3).

The viral vectors examined in this study were based on adeno-associated viruses (AAV) and lentiviral vectors. Dual AAV strategies including trans-splicing, overlapping and hybrid dual-vector strategies were investigated. It was indicated that dual AAV trans-splicing and the hybrid F1 phage genome (AK) vectors showed promising results in mouse models with Stargardt disease. This method allowed the vectors to carry and transport the ABCA4 protein to the photoreceptor cells. This indicated a favourable strategy for the treatment of ABCA4-related disorders. Many trials were thus performed using this model which proved that retinal therapy using the dual AAV model is safe and effective for treatment in ABCA4. The other viral vector considered was lentiviral vectors. Lentiviral vectors were considered beneficial as a vector for ABCA4 as it has the capacity to carry large expression cassettes as that of the ABCA4 protein. Lentiviral vectors are also able to transport genes steadily into its target genome. Lentiviral vectors however did not show much improvement for the treatment of ABCA4 in rodent models which caused this method to be less reliable. However, studies done in non-human primates, such as macaques, showed better improvement. The studies performed in non-human primates indicated that was an improvement in the affected photoreceptors. Although this is promising for possible lentiviral vector usage in humans, more research would need to be done to ensure its safety and efficacy.

This study showed that although extensive research is being done to find the best treatment for ABCA4-related disorders, more still needs to be investigated before a definite decision can be made. It is important to continue research in this area especially as ABCA4 disorders are the most common retinal disorder of mendelian inheritance.


  1. Rahman N, Georgiou M, Khan KN, Michaelides M. Macular dystrophies: clinical and imaging
    features, molecular genetics and therapeutic options. Br J Ophthalmol. 2020;104:451–60.
  2. Roberts LJ, Nossek CA, Greenberg LJ, Ramesar RS. Stargardt macular dystrophy: common
    ABCA4 mutations in South Africa–establishment of a rapid genetic test and relating risk to
    patients. Mol Vis [Internet]. 2012 Feb 1 [cited 2022 May 11];18:280–9. Available from:
  3. Auricchio A, Trapani I, Allikmets R. Gene Therapy of ABCA4-Associated Diseases. Cold Spring
    Harb Perspect Med [Internet]. 2015 May 1 [cited 2022 Sep 16];5(5). Available from:

Treating depression using genes…

by Sethu Poswa

Let us set the scene, an individual has just been diagnosed with depression, making them part of the 280 million other people who suffer with it worldwide. Should they decide to go on treatment, the next step would involve the healthcare professional selecting the appropriate treatment for them, which should be easy right? Wrong. Often times patients are subjected to clinical trials which is based trial and error to find the appropriate treatment. The problem with this method is its inefficiency, in that treatment only starts to work after 4-6 weeks of the trial and during that time period, there is no reliable way of predicting whether the patient will respond to the treatment or whether they will experience drug-induced adverse events, starting the entire process from scratch until appropriate treatment is determined. The danger with this is that recovery is delayed, and the patient may prematurely stop taking medication. Fortunately, pharmacogenetics provides a potential tool in successfully predicting treatment response. 

With National Mental Health Awareness Month approaching soon in October, it is only appropriate that we discuss the steps being taken by science to improve the clinical outcome of patients suffering from depression. Pharmacogenetics studies how an individual’s genetic make-up affects their response to drugs (in this case, SSRIs) and aims to improve disease outcome while preventing the occurrence of drug-related adverse events such as suicide attempts. The most commonly prescribed class of antidepressants are the selective serotonin reuptake inhibitors (SSRIs). This is because SSRIs such as citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline display efficacy and are generally tolerable. Although SSRIs are commonly prescribed, there has been variable responses to them, with only about 33% of people on treatment experiencing an effective response to SSRIs. It is estimated that genetic factors account for approximately 42% of the variability in response to SSRIs, which is why pharmacogenetic studies mainly analyse the genes involved in the metabolism of SSRIs.

SSRIs work by reducing the reuptake of the neurotransmitter serotonin by the presynaptic neurons and it does so by inhibiting the serotonin transporter (SERT). This results in serotonin remaining in the synapse for an extended period of time so that it can act even more on the postsynaptic serotonin receptors. In the past, it was hypothesised that depression was caused by lower levels of serotonin in the body, but modern scientific literature rejects that hypothesis, although it is interesting that literature has observed that people whose serotonin levels have been increased by SSRIs showed improvement with regards to experiencing symptoms. It is also worth mentioning that serotonin plays a role in mood regulation so that feelings of anxiety and depression are reduced within an individual.

SSRIs are mainly metabolised by the enzymes cytochrome P450 2D6 (CYP2D6) and CYP2C19 and is transported by P-glycoprotein (P-gp). CYPD2D6, CYP2C19 and P-gp are encoded by the CYP2D6 gene, the CYP2C19 gene and the ATP Binding Cassette B1 (ABCB1) gene, respectively. Genes have a reference nucleotide sequence and differences from those reference sequences among individuals are referred to as polymorphisms. Polymorphisms exist in different forms such as insertions/deletions, length variation, single nucleotide polymorphisms (SNPs), etc. with some polymorphisms being beneficial while others have detrimental consequences. All of the different polymorphisms of a particular gene forms different versions of the same gene namely, alleles.

Polymorphisms typically alter the structure of the protein for which it encodes, which results in altered protein function. A polymorphism can either affect enzyme activity and/or expression. Polymorphisms in the highly polymorphic CYP2D6 and CYP2C19 genes can determine an individual’s ability to metabolise SSRIs. An individual can be a poor (PM), intermediate (IM), extensive (EM) or ultrarapid metabolizer (UM). Literature has reported that UMs relates to the number of copies of the CYP2D6 gene that a person possesses while PMs are associated with the possession of alleles that are known to correspond with decreased or deficient CYP2D6 activity. UMs are going to display no response to a standard dose of SSRIs since UMs display a high enzyme activity and so UMs will have low concentrations of the drug and its active metabolites, meaning they will experience no effect from the SSRI. On the other hand, UMs are also at risk of SSRI toxicity since active metabolites can accumulate in the body, leading to adverse drug reactions (ADRs) such as the development hypertension or anxiety. PMs are will inefficiently convert the parent drug to its active metabolite, and they will therefore not respond to treatment and are at risk of the toxic accumulation of the parent drug in the body as well experiencing more side effects such as nausea, diarrhoea, etc. 

Literature has reported that IMs for CYP2D6 have shown better response to antidepressants, while UMs have been associated with a higher risk of not responding to treatment and higher suicide cases. PMs and IMs of CYP2D6 or CYP2C19 were reported to experience more severe side effects and side effects occurred the most in individuals with these metaboliser statuses. PMs of CYP2D6 and CYP2C19 have also been linked to having higher plasma concentrations of the parent drug. 

The same pharmacogenetic principles can be applied to the ABCB1 gene, which encodes for P-gp. P-gp is a transporter protein that limits drug intake of certain drugs into the brain by active transport and therefore plays a role in regulating the availability of SSRIs at the brain, which is the action of site of SSRIs. A polymorphism in the ABCB1 gene could result in increased/decreased P-gp expression or increased/decreased functioning. This means that either more or less SSRIs will be removed from the brain, and this will affect the treatment outcome. Resistance to SSRIs is hypothesised to be linked to P-gp hyperactivity, by removing a large enough concentration to have no effect on the patient. Other polymorphisms in ABCB1 have also been linked to treatment response as well as a decreased/increased occurrence of side effects, depending on whether the SSRI is a substrate of P-gp, which includes fluoxetine, citalopram, sertraline fluvoxamine and paroxetine.

With pharmacogenetics being a relatively new field in science, there is still a lot more knowledge to harvest, for example, the physiological role of several genes are unknown as well as the mode of action of a high proportion of drugs, including antidepressants. Of course, pharmacogenetics cannot be the only tool used to determine what antidepressant would be safe and affective for an individual to use., as there are other factors to take into consideration as well as epigenetics. For example, gene and environment interactions have to be taken into consideration, as well as drug-drug interactions, because the patient could also be on medication that is metabolised by CYP2D6 or CYP2C19, for example and they could potentially be potent inhibitors of those enzymes and affect the efficiency with which the SSRI is metabolised. Believe it or not, but an individual’s ethnicity will also affect their metaboliser status since the alleles that determine metaboliser status as well as P-gp functioning are distributed differently, depending on what population the person is part of, for example, approximately 5-10% of people who are of European descent are PMs of CYP2D6 and it is rarer in people of African and Asian descent (approximately 3%) in non-European populations.

The field of pharmacogenetics is providing valuable information that is sure to become even more valuable in the future as technologies develop and more is known about how xenobiotics interact with biological systems. This information will help improve clinical outcomes in an efficient and less intrusive manner.


Bertilsson, I., Dahl, M. and Tybring, G., 1997. Pharmacogenetics of antidepressants: clinical aspects. Acta Psychiatrica Scandinavica, 96(s391), pp.14-21.

De Vane, C.L., 1999. Metabolism and Pharmacokinetics of Selective Serotonin Reuptake Inhibitors. Cellular and Molecular Neurobiology, 19.

Fabbri, C., Di Girolamo, G. and Serretti, A., 2013. Pharmacogenetics of antidepressant drugs: An update after almost 20 years of research. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 162(6), pp.487-520.

Fabbri, C., Minarini, A., Niitsu, T. and Serretti, A., 2014. Understanding the pharmacogenetics of selective serotonin reuptake inhibitors. Expert Opinion on Drug Metabolism & Toxicology, 10(8), pp.1093-1118.

Hirsch, M. and Birnbaum, R., 2022. Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. Medi Media, [online] Available at: <https://www.medilib.ir/uptodate/show/14675&gt;

 Porcelli S., Drago A., Fabbri C., Gibiino S., Calati R., Serretti A., 2011. J Psychiatry Neurosci 2011;36(2):87-113, DOI 10.1503/jpn.100059

Ramsey, L., Bishop, J. and Strawn, J., 2019. Pharmacogenetics of treating pediatric anxiety and depression. Pharmacogenomics, 20(12), pp.867-870.

Rybakowski J.K., Serretti A. (eds.), Genetic Influences on Response to Drug Treatment for Major Psychiatric Disorders, DOI 10.1007/978-3-319-27040-1_3

Zobel, A. and Maier, W., 2010. Pharmacogenetics of antidepressive treatment. European Archives of Psychiatry and Clinical Neuroscience, 260(5), pp.407-417.

Data Visualization for Biologists

by Precious Kunyenje

Data visualization is a graphical representation of information and data by using visual elements like charts, graphs, and maps. It makes data easily accessible, provides an understanding of trends, outliers, and patterns in data, and makes it easier to share information.

Different data visualization tools and software are available for use by biologists. They are used to analyse and present biological data in visual formats.

The commonly used data visualization software by biologists includes SPSS, STATA, Excel, RStudio, and Python. Other data visualization software used by biologists include Graphpad Prism, Eviews, NVivo, and ATLAS just to mention a few.

Most data visualization tools and software come with resources on how to use them for analysis and data presentation. These are useful and a more convenient way to familiarize yourself with the tools and software on your own. The following are links to the resources for the frequently used data visualization tools and software.

  1. SPSS
    SPSS is a software package for editing, analysing, and visualising data. It is used for
    statistical analysis of all sorts of data including from scientific research and provides
    the results in visual formats. To know more about SPSS, use the following link:
  1. STATA
    STATA is a statistical software package for data manipulation, visualisation, statistics,
    and automated reporting. It is used by researchers in many fields including
    biomedicine, epidemiology, and science. It is an excellent alternative to SPSS, shares a
    lot of features, and has other additional tools giving it an advantage.
    For an easy guide and introduction to using STATA, use the following link:
    https://data.princeton.edu/stata. It is an introductory tutorial and will get you to know
    STATA in no time.
  1. RStudio
    RStudio is an open-source integrated development environment that facilitates
    statistical modelling as well as graphical capabilities for R. It is integrated with a lot of
    statistical and analytical packages for managing biological data.
    It is an excellent data visualization software for biological scientists. The link below will
    provide guidance to understanding RStudio and R programming: https://dataflair.training/blogs/rstudio-tutorial/.
  1. NVivo
    NVivo is a good data analysis and visualization software for qualitative research. It
    helps qualitative researchers organise, analyse and find insights in unstructured or
    qualitative data like interviews, open-ended survey responses, and journal articles.
    NVivo handles virtually any data, including Word documents, PDFs, pictures, database
    tables, spreadsheets, audio files, and videos. You can display connections, ideas, and
    findings using a range of visualization tools such as charts, maps, and models, and you
    can easily view the live data behind them. To learn more about NVivo, use the following
    link: https://tc.instructure.com/courses/7395.

There are many software packages that can be utilised by biologists for data analysis and visualisation. It is important for biologists to know the type of data they are using and their intended outcome. This helps make better decisions on which software package to use for data analysis and visualisation. All software packages cannot be
exhausted in this single blog, there are many amazing data visualisation software with cool features, all to be explored!


Beware of the ‘Silent killer’ that is ravaging lives in South Africa

by Siphenathi Ntoba

Do you know about your blood pressure levels? Many were murdered obliviously by this ‘silent killer’ disease. Hypertension (HTN) is a multifactorial (involves genetic and nongenetic factors) condition, characterized by persistent elevated blood pressure (BP) against blood vessels. It is a risk factor for heart disease. HTN grade1 (Systolic BP: 130–139 mmHg and Diastolic BP:80–89 mmHg), and HTN grade2 ≥ 140/90 mmHg (SBP/DBP).

Globally, 1.39 billion adult people are hypertensive and 10.4 million deaths worldwide. HTN has remarkable increased prevalence in Sub-Saharan Africa resulting to a rise of premature deaths. In South Africa, HTN has drastically enhanced as a great burden with 27-58% of prevalence.

The writer seeks to provide knowledge and awareness of the risk factors of ‘silent killer’ (no obvious symptoms)- hypertension. HTN is influenced by genetics, sociodemographic, and lifestyle behaviors. Physical inactivity and unbalanced food have great influence on HTN development and progress. Body mass index (BMI) is known to be the number one prompting factor of HTN which is associated with type 2 diabetes mellitus development (T2DM– 2xmore risking factor for HTN). It was reported that most rural people of Mthatha were unaware of their T2DM due to their unavailability for diagnosis hence they were victims thereof.

Most studies revealed that blood pressure (BP) is poorly controlled due to unknown HTN status, hence untreated regardless available resources for such responsibility. South Africa found it challenging to manage overburdening of HTN and its complication while experiencing poverty, increase in unemployment, socio-economic inequality, and its apartheid history. Cultural observance and masculine stigma have caused men to be victims of HTN.

Therefore, HTN prevalence has drastically increased due to the mention risk especially BMI and unbalanced diet. The best way to prevent and treat HTN requires an individual diagnosis and adherence to medication when applicable and being physical active.


Sharma, J. R., Mabhida, S. E., Myers, B., Apalata, T., Nicol, E., Benjeddou, M., Muller, C., & Johnson, R. (2021). Prevalence of Hypertension and Its Associated Risk Factors in a Rural Black Population of Mthatha Town, South Africa. International journal of environmental research and public health, 18(3), 1215. https://doi.org/10.3390/ijerph18031215

No pressure

by Tasneem Toefy

As many of you very well know, the period from the year 2020 up until now had been a real nightmare. While I won’t dwell on the dreaded p-word (if you aren’t thinking “pandemic”, then you’re my type of person), I would like to reflect on my experience academically from thereon.

My postgraduate journey had a rocky start. I graduated with a Bachelor of Science degree in Human anatomy and physiology (commonly known as “HUB” at the University of Cape Town), only HUB. Just one major, because I was too disinterested in anything else like Biochemistry or Genetics (no offense to those of you studying it now, I’m sure it’s great – for you). And as you can imagine, this created some pause to my then plans. You see, I had hopes of diving into the workforce after graduating, possibly interning at some medical laboratory or clinical company where I could wear a lab coat or scrubs and gain in some more practical experience. I mean, there’s absolutely nothing wrong with opting out of postgraduate studies; however, I’ve come to understand that here, in our lovely South Africa, there’s not much available to those in medical science who haven’t specialised. Having only an undergraduate degree, specifically in science, has become the equivalent of having a matric certificate (i.e., National Senior Certificate). Besides that, being in the midst of a pandemic and related lockdown reduced my chances of getting in anywhere to basically zero, as job opportunities decreased to remarkably low levels. And that’s how, in 2021, I found myself lying in bed every day roaming through shows on Netflix, wallowing in self-pity and wondering what I was going to do with my life. I eventually, after putting things into perspective once I remembered that there were people poverty-stricken or abused elsewhere, I accepted that I shouldn’t waste the opportunities I could have access to. And off to postgraduate studies I went, enrolling at UCT for an Honours in Biological anthropology in 2022 – the year of adaptation (you see what I did there? I just used some human variation jargon I learned this year). No, this programme was not a dream of mine, nor was it what I was expecting to go into when I toyed with the possibility of furthering my studies. It’s become more than that – I not only learnt more than I could have imagined, but also grew as a person.

I don’t have much else to elaborate on, nor do I have monumental words of assurance, but what I can leave you with is that what life has taught me lately is to be understanding of yourself. There isn’t a set way to live your life, so don’t pressure yourself to meet certain self-stipulated deadlines. It’s okay to not know what you’re doing sometimes; you’ll figure out what’s best for you and when the time’s right to do so. If life gives you lemons, there are many other things to make besides lemonade (just saying).

The beginning of postgraduate studies

by Kristen Sandys-Thomas

Honours is a super fun year! What I love most about it is that we are physically contributing to the body of science through our research projects and this is how it’s so different from undergrad studies. I think it’s really important to go into honours with a positive mindset and aim to work hard (during modules and the research component). The year goes really quickly so I think the best advice is to try and enjoy every component of the course as it is not a long and recognise that we are very privileged to be studying at the Health Science Faculty. You will meet a lot of really nice people in the course (your class mates, your supervisors, and professors). Don’t stress that we have transitioned to face-to-face (F2F) learning and F2F exams. F2F has been so much better than online learning and it helps you to feel more comfortable with the course, your supervisors and your peers. It’s also really nice to be on campus and see that campus as for the most of us it’s a new campus, and it’s nice meeting your professors in person rather than via a computer. Exams were also not bad this year even though they were F2F and I was super nervous as the last time I wrote a physical exam was in 2019 (3 years ago). Modules are intense as it’s only three weeks per module for course work and we write an assessment at the end of each module – this is great because it forces you keep up to date and not fall behind so that you are prepared for exam week.   

Don’t stress if you don’t get your project of choice – I guarantee you, whatever project you land up with you are going to meet some really awesome, intelligent people who are going to inspire you in one way or another. I came into honours having the expectation that I would not enjoy research. It took me a bit of time this year to start getting comfortable with research,  lab work, and reading lots of articles & getting familiar with my research field, but once you reach a level of confidence you begin to realise that the life of a researcher is rather nice. I plan to do my MSc next year, here at UCT, where we will look at next generation sequencing data of 2 twins who experienced an ACL rupture, and through the use of bioinformatic analysis we hope to underpin the genetics of ACL rupture or get closer to unravelling the genetics of ACL rupture.

Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1

by Luca Bell

Conventional T cells recognise peptide antigens presented by major histocompatibility complex (MHC) molecules, Human Leukocyte Antigen (HLA) molecules in humans. Unconventional T cell clones bind antigens restricted by MHC related protein 1 (MR1). Such cells, MAIT cells, are documented as recognising metabolic intermediates as antigens presented by MR1.

A group of researchers from around the globe reported a T cell receptor that recognised cancer cells and promoted cell lysis, while not recognising healthy cells. They also sought identify the mechanism of this selection. The T cells reported by the authors showed no difference in targeting engineered cancer cells that lacked peptide presenting molecules. This was similar to MAIT cells.

Peripheral blood mononuclear cells (PBMC) were isolated from blood by centrifuge and then cultured with lung carcinoma cells for two weeks. Primed PBMCs were cloned. These T cells are referred to as MC.7.G5. Embryonic kidney cells from the HEK293T cell line were transduced with a library of single guide RNAs (sgRNA) targeting all protein coding genes in the human genome. These sgRNAs direct the Cas9 nuclease to splice out the gene targeted by the sgRNA. This results in a library of HEK293T cells that each have a gene removed. These cells were incubated along with the MC.7.G5 T cells. HEK293T cells that survived were resistant to lysis by the MC.7.G5 T cells. The HEK293T cells were collected, and their DNA was isolated and sequenced using Illumina sequencing. These reads were compared to a control sample of HEK293T cells that were not incubated with MC.7.G5 T cells. sgRNAs that were enriched compared to the control indicated genes that were spliced out and resulted in increased survival. These genes are thus important for recognition by T cells.

The genes important for T cell recognition were found to encode proteins involved in promoter activation of MR1 and β2M, with which MR1 forms a dimeric antigen-presenting molecule known to activate MAIT cells and other T cells. MR1 being the primary antigen presenting molecule in the targeting of cancer cells by T cells was confirmed by a loss-of-function assay.

MC.7.G5 T cells were shown to decrease the Jurkat leukaemia cell burden in mice by an average of 95% compared to the control, after 18 days.

Benefits of MR1 as an antigen presenting molecule are that, unlike HLA molecules which are highly polymorphic and are present polymorphic peptide antigens, MR1 is monomorphic and presents non-peptide antigens.

In order to test the safety of MC.7.G5 T cells as a treatment, the T cells were incubated with healthy cells of different tissue types that had been stressed or infected with pathogens. MC.7.G5 T cells were found to be inert.

The take home message of this study is that MC.7.G5 T cells are an example of a potential cancer treatment that, unlike chemotherapy for example, does not target healthy cells as an adverse side effect and can be used to treat any human, regardless of their HLA genotype.


Crowther, M., Dolton, G., Legut, M., Caillaud, M., Lloyd, A., Attaf, M., Galloway, S., Rius, C., Farrell, C., Szomolay, B., Ager, A., Parker, A., Fuller, A., Donia, M., McCluskey, J., Rossjohn, J., Svane, I., Phillips, J. and Sewell, A., 2020. Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. Nature Immunology, 21(2), pp.178-185.

Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future?

by Jesse Conradie

Fecal microbiota transplantation (FMT) has proven to be an effective treatment in recurrent Clostridioides difficile infections. Long term side effects have not been established to date. The direct link between the gut microbiota and almost 95% of human disease has raised interest in the therapeutic application of FMT for the treatment of autoimmune, metabolic etc., disorders not previously linked with the gut microbiome. However, although FMT is considered safe in the long run, minor short term adverse effects from the procedure include transient diarrhea, abdominal cramps, fever, constipation. Although FMT is considered safe and well-tolerated in high-risk individuals, much research is still required before FMT can be established as an accepted therapy. Special consideration should be given to the current COVID-19 pandemic, as the SARS-COV-2 virus has recently been found to be present in the stool of infected individuals. This raises concerns about whether the oral-fecal transfer of SARS-COV-2 and other pathogenic microorganisms is possible. Therefore, the screening for SARS-COV-2 antigens should be added to the already established screening protocols before FMT treatment, and this would most likely include additional antigens as more pathogenic microbes emerge.

Although many studies have shown that the benefits of FMT outweigh the minor short-term risks, there still needs to be consideration when it comes to patients themselves, as the transplant of fecal matter from donors to recipients is not generally considered favourable. At the current moment, not many individuals outside of the world of science seem to be aware of the benefits of FMT, the future use of this technique in the treatment of many human diseases requires more public engagement and spreading of information regarding its safety and benefits.


Hanssen, N.M.J., de Vos, W.M & Nieuwdorp, M. (2021). Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future? Cell Metabolism, 33. https://doi.org/10.1016/j.cmet.2021.05.005

Park, S & Seo, G.S. (2021). Fecal Microbiota Transplantation: Is It Safe? Clin Endosc, 54. https://doi.org/10.5946/ce.2021.072


Grateful for 2022

by Tayla Kebonte

Being a part of the honours Neuroscience & Physiology class of 2022 has been a great privilege. My curiosity about the brain and its mysterious workings has been nourished by lecturers and my peers. I particularly enjoyed the Advanced Cellular Neuroscience module – I felt that I was learning something completely new every day which was thrilling (though the complexity of what I was learning daunted me at times).

Initially, I started the year with the intention of taking up a research project that was clinically oriented but after a quick mental pep-talk I realised that I only have 1 year to be completely immersed in all-things-neuroscience. I reasoned that I would benefit from learning skills and techniques that I would not learn in medicine. So I sit here (several failed qPCRs and tissue cultures later) to say that I feel more equipped than ever to be a functional member of a lab.

I have enjoyed being a part of the O’Ryan lab – working with a group of patient, intelligent and hardworking women has urged me to be just the same. The contribution this lab has made to autism genetics is incredible! I am eager to see what the future holds for this group.

One particular skill that I am particularly grateful for is my newfound ability to critically read scientific papers. It is a priceless skill! So priceless that if the entire year consisted of reading and writing only, I would have benefitted greatly still.

All-in-all, taking a year out of medicine to do this was entirely worthwhile.

Defining my future clinician-scientist career on my own terms

by Asande Vilane

At the beginning of last year, myself and a number of my 3rd year MBChB peers enrolled into the Molecular Medicine program: an adjunct course which aims to give aspiring clinician-scientists a background in basic science knowledge and techniques. This journey has since taken us into the honors year, and has seen us undertake introductory research courses in fields such as Neuroscience and Physiology, Infectious Diseases and Immunology, Genetics, Bioinformatics, and Molecular Cell Biology. This experience, which has gifted us with experience both in the clinical and lab platforms, has prompted me to continuously revisit and redefine the term ‘clinician-scientist’.

From a distance, it’s easy to define what a clinician-scientist is: a person with training in both the clinical and science-based fields who combines their skills to conduct research in a way that relates to human health and disease. In my late high-school years, this concept seemed flawless. Yes, I wanted to be the person who had seen, firsthand, the clinical problems that I wanted to solve – and I believed was going to seamlessly transition from my patients to the bench every day with the glamour and flair of a reality-tv show main character (also why isn’t this already a show?). As I’ve grown (a little) older and have had the privilege of enrolling in the BMedScHons (infectious Diseases and Immunology) program, parts of my preconceptions have been both reinforced and shattered by my experiences.

Firstly (and I was actually asked this in a casual interview) – what’s the real need for a clinician-scientist? And why do I want to become one? While it’s true that we need people who can speak both languages to bridge the gap between science and medicine, thus driving the creation of valuable translational research, we also need to keep in mind that we have scientists… and we have doctors. And sometimes, with enough continued education, they can indeed speak each other’s language. So what exactly is the need for someone with an all-round training? Where does this person fit in the grand scheme of things – or what exactly is the problem that they are trying to fix? It becomes difficult to answer these questions without all the buzzwords.

Secondly – what is a clinician-scientist in the South African context? Unlike developed countries which have established MD PhD or MBChB PhD tracks which produce graduates that are quickly zapped up into biotech and big pharma – the idea of this joint training is still quite new in South Africa’s history. While there remains space for one to innovate in corporate medicine using these skills from training, one will have to face the inevitable question of how they will spend their time and their skills once they graduate. Are you going to specialize, and sacrifice the time you could have been using for research? See patients full time and treat your lab work as a fever dream? As a person who came into medicine fully convinced that I’d end up as a full-time basic scientist, this question becomes difficult to answer once you get your first taste of the clinical realm.

Lastly, why do I want to become a clinician-scientist? It’s no secret that medical students are notorious careerists – and being forced to truly reflect and ponder on this question while consciously removing that old high-school identity as an ‘achiever’ has been an interesting experience.

I can’t, however, explain this answer without talking about Angela Merkel. Now the former chancellor of Germany, Angela Merkel has a PhD in quantum chemistry – but also succeeded in becoming a leader while campaigning under a conservative party. While I was already reading biotech articles at 4am way back when – Angela convinced me that being a leader and being a thinker and innovator are not and have never been in antithesis to each other. While my greatest aspiration remains to leave a positive impact on our society, I’d be lying if I didn’t mention that this has also been a journey in the exploration of self. Apart from trying to develop myself along the thinkers as leaders paradigm, being a clinician-scientist also seems to be allowing yourself to develop your career on your own terms. While it’s scary that this is a new South African phenomenon, and there’s no telling exactly how you’ll use your skills – it’s also warming to know that this journey is yours to define. That you don’t have to have all the answers just yet, and that it’s enough to follow an urge or a passion. That for now – it’s enough to be an experience experiencing experiences.

The only way I can describe my honours year is a rollercoaster: there have been moments where I’ve strolled into the Institute of Infectious Diseases and Molecular Medicine (aka the IDM) fully convinced that I’m where I’m supposed to be, and feeling refreshed by the change of pace from the medical program.. but there have also been days where, after over a month of repeating the same experiment, I wished I could just go see a patient and give them antibiotics and know that they’d be on the up and up three days from now. These experiences have all been part of the process, and have been instrumental in teaching me to experience things in the moment, to take a critical look at old decisions and preconceptions, and to allow myself to explore a little – regardless of how it will turn out.

Reawakening of insulin production in Pancreatic cells from Type 1 Diabetes (T1D) donor patient

by Nimra Khan

The global disease burden of diabetes is 536.6 million people worldwide. Diabetes can be divided into Type 1 and Type 2 diabetes mellitus. Type 1 diabetes (T1D) is an autoimmune disease that destroys insulin-producing Beta (β) cells in the pancreatic islets (Figure 1). Insulin is a hormone made in your pancreas; a gland located behind your stomach. Insulin allows your body to use glucose for energy. People with T1D rely on daily insulin injections to replace what would have been produced by their β cells. Complications related to diabetes includes an increased risk of cardiovascular disease, kidney failure, heart attack, stroke, lower limb amputation, nerve damage and vision impairment. Current strategy of replacing the damaged β-cell mass involves whole pancreas transplantation. Because of a shortage of organ donors and problems associated with immunosuppressive drugs, transplantation strategies have limited clinical use. Therefore, looking at the possibility of regenerating β-cells in the pancreases is of interest.

Intriguingly, the human epigenetics research team from Monash University in Melbourne, Australia was able to “reawaken” stem-like cells in the pancreas and re-establish insulin expression from those cells using a drug approved by the US FDA. The research team published their findings in the article “Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor” in Signal Transduction and Targeted Therapy.

Experimental evidence shows inherent plasticity (ability to change function) of pancreatic cells, this fuelled interest in the potential regeneration of β-cells from other pancreatic cells (Figure 1). This potential regeneration of β-cells was previously demonstrated with the discovery of Alpha (α) cell plasticity and the ability of ductal and α-cells to convert into insulin-producing cells in the pancreases. It is also important to understand that the pancreas showed classic silencing of β-cell progenitor (ancestral) genes with barely detectable insulin transcript. This default silencing occurs due to EZH2 gene’s methyltransferase protein activity on H3K27me3. H3K27me3 is an epigenetic modification to the DNA packaging protein called Histone 3, this moditification functions to silence the insulin gene using EZH2 protein.

Therefore, the objective of this study was to investigate the effect of the drug GSK126 on the specific regulation of the H3K27me3 activity by EZH2 protein that is considered responsible for default suppression (transcriptional gene silencing). The overcoming of this suppression is critical to the progenitor cell’s developmental programme by enabling them to differentiate into functioning insulin secreting β-cells.

Isolated cells derived from the pancreas (Figure 2) were stimulated with GSK126 – a specific pharmacological inhibitor of EZH2 gene’s methyltransferase protein. Results showed that the drug effectively reduced h3k27me3 content, thereby influencing beta cell plasticity and promoting insulin gene expression (Figure 3). GSK126 also reinstated Insulin gene expression despite absolute β-cell destruction, dramatically influencing insulin expression in diabetic donor cells with damaged pancreatic islets. Treating the ductal cells with the drug GSK126 caused them to functionally resemble β cells and to produce insulin. These results showed a promising future for T1D treatment.

The main advantage of this method of treatment over beta cell replacement includes rapid insulin restoration requiring several days of drug treatment only as opposed to other protocols that can take several months. This novel research approach would allow insulin-producing β cells that are destroyed in T1D patients to be replaced with new insulin-generating cells. An important step towards developing new therapies.

Concluding remarks and future perspectives

Diabetes affects millions of people worldwide, this research is a starting point towards aiming to improve the quality of life of individuals with diabetes by reducing the need for insulin injections, dietary and activity restrictions, and importantly eliminate the need for pancreas transplants in chronic sufferers. These scientists discovered a way to “awaken” stem cells in the pancreas and harness their ability to express insulin.

Why is this discovery important? Because this provides a potential for treatment whereby using the patient’s own pancreas cells we can turn on genes which promote the production of insulin and will ultimately reduce the dependency on insulin injections (up to 100 per month) and eliminate the need for pancreas transplants. 


Al-Hasani, K., Khurana, I., Mariana, L., Loudovaris, T., Maxwell, S., Harikrishnan, K. N., Okabe, J., Cooper, M. E., & El-Osta, A. (2022). Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor. Signal transduction and targeted therapy7(1), 248. https://doi.org/10.1038/s41392-022-01034-7

Healthline. (2019). 10 Facts About Type 2 Diabetes and Insulin: Types, Risks, and More. [online] Available at: https://www.healthline.com/health/type-2-diabetes/insulin-facts-to-know#habits [Accessed 16 Sep. 2022].

Far from Home

by Precious Kunyenje

Listening to good girl by Lucky Dube with my father while he escorted me to the airport, is but the last memory I have from home. Where his words could not reach, music was the way he could explain what was in his heart. The mixed emotions he had, being proud of his child’s success for being admitted to the best university in Africa and the fear of letting the child go into the unknown was all I could understand from the song. We spoke less but we knew we would miss each other.

Looking back, it’s been almost a year now since we saw each other, and I miss my family. It has been quite an experience being far from home and living in Cape Town. While fear was certain, the excitement of being in a new school, a new city was amazing. I love the environment, the school, and the friends I have made along the way. Life has ups and downs, and I have had my bad days through this period. Academic stress, financial hardship, homesickness, and loneliness have been part of my life, but I am grateful to the UCT family, my friends, and my lecturers for their continuous support. Without them, it could have been a living hell staying in Cape Town.

Being away from home and from people, you used to see every day can be challenging. But sometimes to grow, we need to come out of our comfort zone and grab the opportunities provided to us by life. I am happy I took this opportunity to come to UCT and have this wonderful experience.

Autism – Should We Be Leveraging Neuroplasticity?

by Talya Kebonte

Can you imagine a world where you aren’t able to pick up on the emotions of people around you? What would it be like if you couldn’t sense the sombre mood of a vigil and burst out into belly laughs while everyone around you was mourning? What if every piece of clothing you wore felt like sandpaper against your skin? How lonely would you feel if people labelled you as ‘weird’ and chose to avoid you? These are some of the things that a person with autism experiences.

Autism Spectrum Disorder, commonly referred to as autism, is a lifelong disability that affects one’s ability to communicate with people. It also causes problems in how one senses things [1]. Autism can be diagnosed as early as 18 months but is not usually diagnosed earlier than the age of 3 [2]. The timing of diagnosis is critical for treatment – an infant brain is more able to change according to experience than an adult brain, in other words, it has greater neuroplasticity [3].

To better understand neuroplasticity, picture the brain as a pastel pink ball of soft clay. When you are born it has a distinguishable shape, but it is still mouldable. The older you get, the more the clay hardens until you can’t change its shape anymore. The idea is to diagnose autism ‘while the clay is mouldable’ so that children can receive therapy and avoid social and sensory challenges that would otherwise be lifelong.

A randomised control trial on a group of Australian infants was done to test whether early therapy improved signs of autism. About half of the infants received 10 sessions delivered in their homes by a trained therapist while the other half received placebo care. After two years, it was found that the infants who received therapy had lower chances of having deficits in social-emotional interactions, repetitive movements, and unusual sensory interests compared to those that received placebo care [4].

Though these results are promising, the effects were small in extent. Hence, the clinical significance thereof is uncertain. It should be noted, however, that these small effects were enduring. Perhaps in the future we will have a more robust understanding of how the brain is ‘moulded’ in this condition and tailor more sensitive therapies for infants with autism.


[1]       L. Naithani et al., “Early Autism Intervention Components Deliverable by Non-specialists in Low- and Middle-Income Countries: A Scoping Review,” Frontiers in Psychiatry, vol. 13. Frontiers Media S.A., Jun. 29, 2022. doi: 10.3389/fpsyt.2022.914750.

[2]       M. van ’t Hof et al., “Age at autism spectrum disorder diagnosis: A systematic review and meta-analysis from 2012 to 2019,” Autism, vol. 25, no. 4. SAGE Publications Ltd, pp. 862–873, May 01, 2021. doi: 10.1177/1362361320971107.

[3]       B. Kolb and R. Gibb, “Brain plasticity and behaviour in the developing brain.,” J Can Acad Child Adolesc Psychiatry, vol. 20, no. 4, pp. 265–76, Nov. 2011.

[4]       A. J. O. Whitehouse et al., “Effect of Preemptive Intervention on Developmental Outcomes among Infants Showing Early Signs of Autism: A Randomized Clinical Trial of Outcomes to Diagnosis,” JAMA Pediatr, vol. 175, no. 11, Nov. 2021, doi: 10.1001/jamapediatrics.2021.3298.

Massive animals may hold secrets of cancer suppression – Peto’s Paradox

by Sibongiseni Msipa

Cancer is a creepy and mysterious thing. While we tried to understand it, to get better at killing it, we discovered a biological paradox that remains unsolved to this day: large animals are immune to cancer. Which does not make any sense – the bigger a being, the more cancer it must have. To understand why, we first need to look at the nature of cancer itself.

To understand the nature of cancer we must first understand how cells work. cells are the basic units that make up the human body. they are made from hundreds of millions of parts. Guided by chemical reactions, they build and break down structure, sustain metabolism to gain energy or make copies of themselves. These complex chemical reactions are called pathways. Pathways are biochemical networks upon networks, which intertwined with each other, and function perfectly – until they do not. With these billions of reactions occurring in thousands of networks over many years, the question is not “if” something will go wrong but when? Tiny mistakes accumulate in the DNA of cells until this “perfect” network of systems gets corrupted. To prevent this from happening our cells have kill switches that make them commit suicide when cells are corrupted, however these kill switches are fallible. If they fail a cell can turn cancerous. Given enough time a cell would accrue enough mistakes, slip by unnoticed and begin to make more itself. All animals face this ordeal.

In general, the cells of all animals are the same size. The cells of a mouse are not fewer than yours, it just has fewer cells in total and a shorter lifespan. Fewer cells and a short lifespan mean a lower chance of things going wrong or cell mutating, – or at least it should mean that. Humans live about 50 times longer and have more cells than mice, yet the rate of cancer in humans and mice is the same. Even weirder blue whales have even more cells than humans, but they do not seem to get cancer at all. This is known as Peto’s Paradox.

Peto’s paradox is the baffling realization that larger animals have much less cancer than they should. Evolutionary biologists think that this results from larger animals using protective mechanisms that many smaller animals do not have. To identify how large animals might foster such mechanisms, evolutionary biologists created a theoretical model to simulate which of 100 possible genetic-mutation strategies would become most prevalent over 4,000 generations. The model included two gene types, Tumour suppressor and proto-oncogenes. The latter when mutated is bad news. For example, with the right mutation a cell will lose its ability to kill itself, another mutation and it will develop an ability to hide, another and it will send out a call for resources and multiply quickly. These genes, however, have an antagonist, known as tumour suppressor gene.

Tumour-suppressor genes, repair cellular damage that could otherwise lead to cancer. They found that tumour-suppressor genes and proto-oncogenes react differently along a gradient of body masses. In this model, evolution always favoured tumour-suppressor genes in large animals. Proto-oncogene activation decreased steadily with increasing body mass; the team found. Because of this, whales require more mutation than mice to develop a tumour, they are not immune but more resilient.

Or the solution to this Paradox may be something different; Hyper tumours. Hyper Tumors are named after hyperparasites, the parasites of parasites, hyper tomours are Tumour-within-a-tumour. Unlike normal cells which work together, cancer cells are selfish and work for their own short-term benefit, when successful, these cells form tumours these are huge cancer collectives which are hard to kill.  These cancerous cells require a lot of energy and resources to continue multiplying rapidly. Therefore, the amount of energy needed by these cancer cells becomes its growth limiting factor.  To counter this the body is tricked into building new blood vessels directly to the tumour, to feed the thing killing it. This is where the nature of cancer cells may become its undoing. Because of how unstable they are they continue to mutate and if they do this for a while one of the copies of the copies of the original cancer cell might suddenly think of itself and stop cooperating and just like that the original tumour suddenly becomes an enemy and blood supply is cut off to the original tumour – this starves and kills the original cancer cells. Cancer is killing Cancer. This process can repeat repeatedly, this then prevents cancer from becoming a problem in large animals. It is possible that large animals have more of these hyper tumours than we realize, they might just not become big enough to notice. So, an old blue whale might be filled with tiny cancers and just not care.

There are other proposed solutions to Peto’s Paradox, such as different metabolic rates or different cellular architecture, but right now we just do not know. Figuring out how large animals are so resilient to this deadliest disease; we might open up a path to new therapies and treatments. Cancer has always been a challenge but today we are finally beginning to understand it and by doing so we will finally overcome it.


Nagy, D., Victor, M. & Cropper H. (2007) Why don’t all whales have cancer? A novel hypothesis resolving Peto’s paradox. Integrative and Comparative Biology, (47)2, pp 317–328

Gewin, V. (2013) Massive animals may hold secrets of cancer suppression. Nature, https://doi.org/10.1038/nature.2013.12258

Scientists on the hunt for new, more effective anti-TB drugs

by Asande Vilane

Note: this blog is based on a 2018 review by Tiberi et al titled ‘New drugs and perspectives for anti-tuberculosis regimens’. It is third on the reference list and is thus indicated by the [3] in text referencing. Information that has been taken from other sources to provide further background information has been cited accordingly.

Above: the discovery of new anti-TB drugs is necessary to fight the threat of this debilitating disease. Faced with a slowing antibiotic discovery timeline, can scientists innovate new ways of addressing this deadly infection? Image taken from: https://www.technologynetworks.com/drug-discovery/articles/expediting-drug-discovery-using-novel-target-based-approaches-357879

In 2020, 1.5 million people succumbed to tuberculosis (TB)[1]. This debilitating disease, primarily affecting the lungs[2], is commonly treated with a six month regimen consisting of four different drugs, but various factors decrease the efficacy of this approach. In addition to issues with compliance, the treatment is not always well tolerated nor well prescribed, and may have devastating side-effects such as damage to the liver[3]. These issues with treatment adherence, tolerability and sub-optimal drug levels can lead to the development of multi-drug or extremely drug resistant TB (MDR and XDR TB respectively). MDR and XDR TB require more expensive, and increasingly toxic treatments, and have poorer outcomes as compared to drug sensitive TB[3]. Keeping the above in mind, scientists from around the world embarked on a non-systematic literature review to assess progress in the search for new anti-TB treatments – with the intention of assessing and highlighting key advances in the search for new anti-TB treatment approaches.

Discovering and isolating and assessing novel compounds for the treatment of TB is notoriously difficult and time-consuming with a high cost and an even higher rate of failure[3]. This, together with the need of for-profit companies to commercialize drugs for profit has led to research and development in this area slowing down in recent years. To date, only eight new drugs are in the pipeline with two having moved into the latter stages of confirmatory studies. Bearing this in mind, researchers [3] turned their attention to existing drugs used in the treatment of other diseases. This approach is advantageous as these drugs have already been tested and approved for their safety in humans and are manufactured at scale, and thus would be quickly available for treatment use.

They found that the leprosy drug clofazimine as well as the carbapenem class of antibiotics are promising drugs for use against TB[3]. In several studies, clofazimine was shown to be able to kill the TB-causing bacteria in the lungs. These results were further supported by randomized controlled trials (trials which tested the effects of clofazimine vs current interventions in a non-biased manner) as well as a meta-analysis (a systematic analysis of all the research on the topic) which reported an overall success rate of 61%. Additionally, clofazimine’s pharmacokinetic characteristics (the drug’s effect on the body), such as its tissue distribution, intra-cellular distribution and prolonged half-life make it a prime candidate for use as part of second line anti-TB treatment. Despite this, side-effects such as skin discoloration and heart conduction issues may hinder its advance to use for drug-susceptible TB.

Carbapenems (antibiotics typically used to treat a variety of other infections) have also shown promising results when used to treat MDR TB[3]. This has been shown by in-vitro activity, case reports and recently promising results from a phase 2b randomized control early bactericidal activity trial. Together, these results have prompted a whole new look at the management of drug resistant tuberculosis and have inspired new and innovative approaches to drug development in the context of TB.

While TB remains a global threat, there are still some promising leads when it comes to pioneering new approaches to treat this disease. Scientists such as [3] have highlighted that even when the search for new compounds becomes elusive, repurposing existing solutions can still offer some hope – paving the way for new frontiers in our clinical approach to tuberculosis disease.


1.         (WHO), W.H.O., Global Tuberculosis Report, W.H.O. (WHO), Editor. 2021.

2.         Pai, M., Behr, M.A., Dowdy, D., Dheda, K., Divangahi, M., Boehme, C.C., Ginsberg, A., Swaminathan, S., Spigelman, M., Getahun, H., Menzies, D., Raviglione, M., Tuberculosis. Nature Reviews: Disease Primers, 2016. 2.

3.         Tiberi, S., Munoz-Torrico, M., Duarte, R., Dalcomo, M., D’Ambrosio, L., Miglioro, G.B., New drugs and perspectives for new anti-tuberculosis regimens. Pulmonology Journal, 2018. 24(2): p. 86-98.

When you become the subject: how to deal with knowing too much

by Anonymous

This reflective piece could give you an additional 5% on your Assignment 2 mark. 5% is not a lot in the grand scheme of things, and yet I found myself ruffling my feathers, so to speak, scrambling for a topic to write about – seeing my classmates have already spread their wings, covering topics such as changing workloads, academic burnout, and the sheer excitement of taking part in studies that feel like they could be from science-fiction movies. Then I realized that I have a different experience that may not be unique but is certainly not commonly discussed: how to deal with knowing too much.

The science field is often seen as a cold an impersonal one, and sometimes it forgets that there are real people behind the sample ID numbers, however, the merit is that we can look at data more objectively as we are not personally affected by the outcome. Whether the experiment fails, or if it turns out to be a flying success, it makes no greater personal difference than moving on or trying again. But now I ask you, what happens when you start seeing yourself, or someone you know in those little numbers?

No one prepares you for the day when you have to present a figure from a clinical trial paper for a cancer treatment, when a family member has just passed away from the exact cancer a new developmental drug is being tested for, or the sadness that comes when you start thinking about all the people who could have lived had this been discovered just a few months earlier. Words fail me when I try to describe what it feels when you’re discussing the merits of a scientific paper with your peers, where one treatment is clearly more effective than another, and the consequent tailspin you get stuck in when you start to doubt your doctor’s decisions regarding your course of treatment – the power that critical thinking holds is a mighty one, and essentially that is what this year is about.

Your honours year is designed to test you and mould you into the future of the scientific world. We are taught how to read critically, how to design experiments and present papers. We are taught how to pipette properly, how to draw graphs and engage with communities – how to translate our research in a way that will allow someone outside our field to understand – and yet we are not taught how to cope with the personal consequences of our research.

For those of you who have resonated with the article and read to the end hoping to see what advice I have, you are not alone. I have more questions than answers, but what I’ve gathered so far is that we should strive to be more like the old Greek figure, Daedalus, who crafted wings of feathers and wax to escape imprisonment. The modern-day equivalent would be to lean into your personal connection to a specific area and let your emotions serve as a source of motivation to honour the field by staying objective, since biased research won’t help anyone in the grand scheme of things. However, and there is a very fine line between passion and obsession and we should try our best not to let our emotions lead us too far astray or we run the risk of following Icarus, who flew too close to the sun.

Discovering bioinformatics

by Alice Piller

As an undergraduate in Genetics and Statistics, I felt utterly torn between the biological side and the “mathsy”, analytical side of science. Of course, that was a naïve view on science as its fields are not discrete but intertwined. I stumbled across a strange new word in my first year of studying from my older sister (who also studied Genetics) – “Bioinformatics” – which stuck with me until my Honours application.

Bioinformatics seemed like the perfect marriage between all my interests. I describe it as the intersection between genetics, computer science and statistics. I was accepted to an Honours in Bioinformatics at UCT and was excited to combine all my interests and skills in one application.

The course was almost entirely online, which I was initially apprehensive about. The bed-to-desk rotation of the last two years of my undergraduate degree was tough, so I was not looking forward to another year of that cycle. To be honest, I didn’t enjoy it this year either. I felt that an important part of university was missing – the lack of engagement with my lecturers and peers. Luckily, there were some in-person aspects, so this year was a huge improvement from the previous two years.

What I found most satisfying about my degree in Bioinformatics is the feeling of being truly interested in a topic and motivated by career options and prospects of the field. I have found working on my thesis highly stimulating and the lectures opened me up to a whole new ecosystem of research. I cannot wait to see where this field takes me!

Precision medicine: how machine learning could change the way we treat cancer

by Alice Piller

Precision medicine is a hot topic amongst the scientific community seeing numerous researchers and practitioners swarm to the field to be at the forefront of this revolutionary concept. Precision medicine is going to change the way we treat diseases by enabling better prevention strategies, hastier diagnoses, quicker recovery, high survival rates, and fewer adverse side-effects. Sounds like a pretty sweet deal worth all the swarming, right? Well, unfortunately precision medicine is not quite a fully-fledged reality yet, but a study on pancreatic cancer [4] conducted by researchers at the University of Cape Town validifies the pursuit of this holy nectareous grail.

While not utilized at its full potential, precision medicine has been put into practice for decades. For example, a person’s blood type is taken into account before receiving a blood transfusion. On a grander scale, precision medicine would see an individual’s genes, environment and lifestyle being considered before administering a treatment. In a few cancer types, genetic markers exist that indicate the cancer’s sensitivity to certain drugs. For example, The KRAS mutation in colon cancer means it will likely respond well to a tyrosine kinase inhibitor drug, and a mutation in ABL1 in chronic myelogenous leukaemia means the cancer is likely going to be resistance to imatinib. [1]

Cancer is currently the second leading cause of death in the world with over 10 million cancer-related deaths occurring in 2019 [2] and a projected 16.4 million deaths in 2040. [3] Current methods for outcome predictions and treatment decisions are largely based on tissues of origin and histological subtyping, leaving vast amounts of informative data unexplored. The researchers at the University of Cape Town lead by Musalula Sinkala, set out to characterise subtypes of pancreatic cancer based on molecular data from cell lines, which could highlight key biological pathways in driving oncogenesis and that could act as potential drug targets.

Sinkala et al. integrated proteomic, transcriptomic, DNA methylation, and miRNA data and identified two distinct pancreatic cancer subtypes, subtype-1 and subtype-2, using a machine learning clustering algorithm. Analysing the attributes of each subtype revealed several critical implications for clinical outcomes, treatment decisions, and drug targets.

Subtype-1 was found to be less aggressive than subtype-2 with a 75% survival rate versus only 35%. A possible reason for this is the increased DNA methylation in genes acting in key pathways including actin cytoskeleton regulation and focal adhesion.

Altered pathways can give great insight into drivers of oncogenesis and potential drug targets. Subtype-1 had hyperactivation and increased protein phosphorylation in the mTOR signaling pathway and displayed evidence of elevated ion channel and secretion pathway activities, whereas subtype-2 displayed hyperactivation and increased protein phosphorylation in cell cycle-associated pathways and elevated peptidase activities. Identification of these altered pathways exposes possible drug targets and, therefore, can help guide treatment decisions. Differential DNA methylation and miRNA signatures were also observed, which could explain the difference in transcriptomic and proteomic profiles of each subtype.

Lastly, the researchers selected a reduced set of 10 mRNA biomarkers and were able to predict drug responses of cell lines, that were not used in training of the model, with considerable accuracy. The reduced set of biomarkers increases this method’s utility in a clinical setting.

Sinkala et al.’s study is a great example of how informative molecular and genomic data can be for improving diagnostic, prognostic and treatment acumen in cancer. The advent of large-scale cell line databases has prompted a shift in the cancer treatment paradigm, away from a “one-size-fits-all” approach to personalised treatment, based on a patient’s unique biological and environmental context. This shift will hopefully see cancer falling from the second leading cause of death to a disease where poor outcomes are a thing of the past.


  1. Testing.com – What are genetic tests for targeted cancer therapy? [Internet]. [updated 2021 May 13; cited 2022 September 15]. Available from: https://www.testing.com/tests/genetic-tests-targeted-cancer-therapy/.
  2. Our World in Data – Causes of Death [Internet]. Hannah Ritchie and Max Roser. [updated 2019 December; cited 2022 September 15]. Available from:  https://ourworldindata.org/causes-of-death.
  3. National Cancer Institute – Cancer Statistics [Internet]. [updated 2020 September 25; cited 2022 September 15]. Available from: https://www.cancer.gov/about-cancer/understanding/statistics#:~:text=Cancer%20is%20among%20the%20leading,related%20deaths%20to%2016.4%20million.
  4. Sinkala M, Mulder N, Martin D. Machine learning and network analyses reveal disease subtypes of pancreatic cancer and their molecular characteristics. Scientific reports. 2020 Jan 27;10(1):1-4.

Protein identification made easy with DeepTracerID

by Awakhiwe Makalima

The success of the human race has largely been owed to our continued efforts in creating ways of getting things done quicker and with more ease. From the healthcare industry, to transportation, to energy… numerous innovations have come about all ultimately making it possible to break barriers as we progress towards a better tomorrow. The field of protein studies has been no exception to this.

Over the past decade advances in electron detection systems and image-analysis software have catalyzed a “resolution revolution” in cryo-electron microscopy (cryo-EM), with the number of structures determined to atomic resolution exponentially increasing each year. Since the cryo-EM approach has less restrictions in terms of sample purity, concentration and volume, these atomic structures have even been determined directly from cell extracts. However, this “flexibility” is where the problem often begins.

Imagine you’re working with Mycobacterium tuberculosis, and you’ve put in a lot of work into identifying an important protein complex involved in bacterial survival within macrophages and its structure has yet to be determined. You’ve gone through a cryo-EM workflow, and you’ve used a software like Relion to obtain a near-atomic resolution cryo-EM map. The issue is you now require additional sequence information of your protein otherwise it will be impossible to build an atomic model. At this point the common solutions to your problem would be techniques, such as tandem mass spectrometry and/or bioinformatics which in the case of the former, would not always be easily accessible nor affordable and with latter the results would not always be easy to interpret.

So how would you identify your protein without the hassle of conducting more expensive and time-consuming experiments? Well, Luca Chang and his team have come up with just the right innovative tool and they’ve called it, DeepTracerID.

This server-based approach first requires the user to input a cryo-EM map which is used to generate a 3D model trace by DeepTracer. The user then needs to input an easily attainable AlphaFold2 protein library of the organism of interest after which three different alignment algorithms can be used to align the AlphaFold2 predicted structures to the generated 3D model trace. The aligned predictions are then statistically scored and listed from lowest to highest score. The correct protein of interest being predicted to be among those with the lowest scores.

The simplicity of this approach has the potential to open doors for incredible breakthroughs in the world of molecular imaging. As we continue to try and better understand the mechanisms via which different biochemical processes occur on a molecular level for various applications such as disease control, it is key for there to be good visual information to study. Continuing with the Mycobacterium tuberculosis example from earlier, it is interesting to see that there are multiple studies which have reported proteomic evidence of thousands of exported proteins, hundreds of which are associated with the strategies the bacterial cells use to survive within macrophages and cause disease. A search on protein data banks however gives nearly zero hits on the structures of these exported proteins nor the membrane proteins which could be implicated in their export out of the bacterial cells. Tools such as DeepTracerID could certainly be one of the keys to making it easier to increase the structural information on protein complexes available to us which is crucial to answering a lot of the questions we have in the research world.


Chang L., Wang F., Connolly K., Meng H., Su Z., Cvirkaite-Krupovic V., Krupovic M., Egelman E.H., Si D. 2022. DeepTracer-ID: De novo protein identification from cryo-EM maps. Biophysical Journal. Volume 121, Issue 15, Pages 2840-2848.

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