An internal pattern of self-doubt that can lead to anxiety, stress and missed opportunities. I’m sure I’m not the only one who has experienced this. Starting my first year at UCT after coming from a different institution was quite intimidating, but the idea of pursuing an honours degree in a subject I knew very little about, seemed almost inconceivable.
Despite my hard work and achievements in undergrad, I often doubted my competence in my field of study this year. Not being the smartest person in the room or having nothing to contribute to a conversation, became the norm. Initially, I viewed this as a negative, but I eventually came to realize that it was actually quite the opposite. I was exactly where I needed to be. Putting myself in uncomfortable situations and environments that allowed for growth and perspective, was one of the smartest things I could do. So, here is some advice that no one asked for, but I’m going to give anyway because I wish I had seen something like this as a reminder before embarking on this honours journey.
Acknowledge your achievements and how far you’ve come. Understand that hard work won’t always lead to good results. Don’t take feedback and criticism on your work personally. A cliché but know that you’re not alone. I can almost certainly say that if you speak to one of your colleagues, you’ll find they’re sharing the same feelings and challenges. Embrace the mistakes and disappointments, don’t dwell on them. Lastly, position yourself to receive what is meant for you.
This year has gone by so fast and although I’m still learning, I know I’ve worked hard and I am qualified to be where I am, sometimes it just takes a reminder or two. I may not be able to replicate my past achievements, but I know that what is yet to come is much greater than what has passed.
Last year around this time I had dreamed of what life would have been like when I had finally been accepted into Honours. I had imagined what a dedicated student I would be and going out and still enjoying time with old and new friends.
Living in that reality now, some of those dreams did not happen. Yes, I try my best to keep up to date with course work and deadlines BUT there is always so much going on and so much to do that I have fallen short at times. When the going gets tough I do try and take a breather just to get back on my feet. Although, I have been told and knew this year was going to be tough, I still went in with an open mind. There have been many challenges along the way, but one can only keep pushing because you only learn from your mistakes.
Besides the millions of things that always have to be done, I am truly enjoying building and gaining knowledge in areas of research that I am passionate about. My eyes have been opened to so many things in this world that I was not aware of. I have also been blessed with an amazing group of friends that have been by my side since we started this year. It feels really great to have built such a strong bond with them, as going into this year I was quite fearful starting a new degree and not knowing anyone.
The feeling of being back on campus and being surrounded by friends has made dealing with everything that is going on, a bit easier to handle. Especially the struggle of loadshedding resulting in my laptop dying during lectures, forgetting my student card and having to call my friends to let me in as well as just having someone to talk to during break times and those late days on campus.
Being back in the laboratory and learning new techniques put me back in my element, I really missed it. I have found my passion with my Research project Team, and I am really excited for what the future holds.
Thus far, the year has been a real learning experience and in this short space of time that has flown by, I have grown so much and have great respect for researchers out there.
There is only a few months left until this academic year ends and I just can’t seem to not feel overwhelmed and excited with a sense of relief. Overwhelmed because of the constant challenges that I have been and currently facing. Excited because I look forward to the new opportunities life has to offer. Relief because the battles is finally coming to an end. Even though the journey thus far has been solely based on my own interpretation of academics, I just can’t seem to only base my whole academic journey on my interpretation. Yes, I tend to interpret academics as soul sucking, but deep down I know I wouldn’t have it any other way. If I’m being completely honestly, I would definitely do it all over again if I had the chance. My interpretation of academics has been my guiding compass, acting as my unique lens through which I perceive the world of learning. At times, it’s been tough, viewing the world of academics as this soul-sucking entity relentlessly demanding my time and effort. Yet, deep down, I acknowledge that this struggle is an integral part of my growth and personal development that has done an excellent job in shaping me into a more determined individual.
The hidden truth most of us students don’t realize is that nothing gives us that insane of amount of motivation than academics, the urge to improve knowledge and skills is something we thrive on. And when that urge the night before an important exam kicks in, we call it the “academic weapon”. I call it the motivation that make us feel more valid and worthy of being called a student in the first place. It’s the driving force that pushes us to unlock our full potential, the eagerness to be better. So yes, let us be “academic weapons”, it’s kind of what keeps us going.
Even through all those late nights, assignment deadlines, extensive reading and exams lead to the most anxiety I’ve ever experienced, there is no doubt that the memories, self-discovery and friendships is something that I will cherish for a very long time. If you are reading this and you feel lost, hopeless, scared or uncertainty, just know that you are not alone. As silly as it sounds, all of this is meant to make you grow, find your way and become a better version of yourself. No one is meant to get it right the first time around. Academics is meant to be an accomplishment, something that is celebrated. So take your time and I’m pretty sure you’ll see the brightest light at the end of the tunnel, not matter how dark and scary that tunnel may look right now.
It is only September 2023, but I already have so much to reflect on. Coming to UCT was scary, being at the “African Harvard school” I had no idea what to expect. I came from a very small institution, so this was a very big transition for me. Big university where I even had to use the shuttles to get to campus, WOW! I was proud of myself for making it here, but I was feeling a little overwhelmed. Not only was I coming to a different school, I was also coming to a new place so I had to adjust to a different environment where I knew no single soul. As if I wasn’t challenged enough, I took on Bioinformatics, I had never coded my entire life, all I really knew were the mere basics of how to use a computer, but here I was. This was beyond my wildest dreams! I took the course with a positive mindset, ready to learn. And let me tell you, this course has exposed me to so many interests I never knew I had. As is I am already looking forward to doing my Masters. I just thought I would do my Honors and that would be it for me but look at me dreaming big. I adjusted so well but this was because my program convener made sure we were all comfortable and at ease, my course mates were also very helpful. I made some very good friends too which is a milestone for my introverted self.
I have made it this far, not feeling overwhelmed but rather empowered. I really feel like I could achieve anything even beyond that which I can imagine. To let you in on a little secret, Bioinformatics wasn’t my first choice but sometimes denial is redirection by God, and I see it now! His plan for me is greater than what I thought possible for myself.
Macy is a 6-year-old girl with microcephaly, a neurological condition resulting in a reduced brain size. Due to her condition, Macy has experienced developmental delays, problems with her balance and coordination, as well as always being the shortest in her class. Since she was diagnosed, Macy’s parents have been asking many questions about her condition, including how it develops and if there are any new advances in microcephaly research that can give them any more information. One of the major limitations in the study of neurological disorders, such as microcephaly, is the lack of a suitable experimental model. Recently, cerebral organoids have emerged as a model for studying neurodevelopment and neurological disorders. These cerebral organoids are created from induced pluripotent stem cells (iPSCs), which can generate any cell type in the human body and are differentiated into small aggregates of neural progenitor cells.
Macy’s parents are well read in the field and were very excited when they came across a paper titled “Cerebral organoids model human brain development and microcephaly” from the Lancaster Laboratory 1 . In this paper, the researchers established a protocol for creating cerebral organoids and have shown how they are able to recapitulate the gene expression of an in vivo brain and they use this to model microcephaly.
The cerebral organoids were generated by providing the iPSCs with very specific culture conditions to direct them to form cerebral tissue (Figure 1). They characterized the cerebral tissue using a variety of different experiments, such as looking at the gene expression of forebrain and hindbrain markers and staining to visualize the localization of these markers. They also stained for specific cell populations, such as neurons and radial glial cells as well as more mature neurons later in the culture period. This confirmed the presence of specific forebrain and hindbrain regions as well as cortical layers in the cerebral tissue. The researchers, however, do make it clear that there is need for further development of the protocol to ensure all brain layers are represented.
Figure 1: Description of cerebral organoid culture system (adapted from figure 1 of the paper)
Next, the researchers used iPSCs, from an individual with a mutation that causes microcephaly, to produce cerebral organoids to model this disorder. As expected, the microencephaly organoids were smaller than controls and the protocol was adjusted to allow them to grow to the same size as controls for easier comparison. Similar experiments were conducted as mentioned above, followed by rescue experiments that involved fixing the mutation to produce normal sized organoids. This confirmed that the microencephaly phenotype was due to the loss of the protein coded for by the mutated gene, leading to premature neural differentiation and a loss of neural progenitors and, thus, a smaller brain size.
This paper is one of the first to show the use of cerebral organoids in modeling brain development and neurological disorders. Research like this gives insight into the pathogenesis of conditions such as microcephaly. It is studies like these that can help answer questions like those of Macy’s parents. They also provide comfort in knowing that we are one step closer to understanding brain development and what happens when this goes wrong!
References 1 Lancaster, M. A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373-379 (2013). https://doi.org:10.1038/nature12517
Have you ever had a gut feeling about something or felt butterflies in your stomach? You are most probably receiving communication from your “second brain”, called the enteric nervous system (ENS).
The ENS consist of two thin layers of nerves that line the gastrointestinal tract all the way from the oesophagus to the rectum. Unlike your central nervous system, the ENS cannot do maths or construct sentences, but is rather involved in controlling digestion.
Scientists call this communication between the gut and the brain, the gut-brain axis (GBA). The communication is bidirectional, linking cognitive and emotional brain centres to intestinal function, implying that your brain will affect the health of your gut and your gut will affect the health of your brain.
In addition to the nervous connection, the gut and brain are also connected by chemical signalling, that scientists refer to as neurotransmitters. The happy hormone, Serotonin, is not just produced in your brain, but is interestingly produced in large amounts by the gut and its microbes. Another neurotransmitter, gamma-aminobutyric acid (GABA), responsible for controlling fear and anxiety is also produced by the gut microbes.
This revolutionized understanding of the GBA paths the way for new treatment options or bowel-disorders, such as irritable bowl syndrome (IBS). Because our two “brains” communicate with one another, therapies that help one may help the other. Antidepressants may be prescribed for IBS patients, not for their mental health but rather because the medication calms nerves in the gut. The use of probiotics and diet has also proved to restore the microbe habitat of the gut. This in turn, have an effect on anxiety, depression and memory function by influencing brain neurochemistry.
In conclusion, the connection between the gut and brain gives us insight on the relation between our physical well-being and mental health. An apple a day may not just keep the doctor away, but your psychiatrist too!
Reference:
Carabotti, M., Scirocco, A., Antonietta Maselli, M., and Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems.
SARS-CoV-2. The virus that has become all too familiar to us since its detection in Wuhan, China, back in December 2019 (Monteil et al., 2022). SARS-CoV-2 spread from country to country like a wave, causing devastating economic, social, and health consequences in every affected region. It instilled fear into every household. Once bustling city streets were suddenly left deserted, as people locked themselves inside the safety of their homes. As the virus swept across the globe, it evolved, resulting in new variants, some more deadly than the last.
Vaccines were speedily rolled out and people lined up to get their jab. Drugs for the treatment of COVID-19, such as antibodies, convalescent sera, and small-molecule-based therapeutics also quickly made their way to the shelves (Monteil et al., 2022). However, there is a problem. The current vaccines and drugs are vulnerable to viral escape mutations (Monteil et al., 2022). Viral evolution has resulted in the emergence of multiple SARS-CoV-2 variants, which have been found to threaten the efficacy and potency of vaccines and therapeutics, as well as influence the infectivity and transmissibility of the virus (Harvey et al., 2021).
There is therefore an urgent need for novel COVID-19 therapeutics that inhibit all current and future SARS-CoV-2 variants to prevent any further damage to lives and economies around the world (Monteil et al., 2022).
Viral evolution of SARS-CoV-2 primarily centres around its Spike protein (Pereson et al., 2021). The Spike protein is essential for the virus to enter the cell. The Spike protein’s Receptor- Binding Domain (RBD) binds to the ACE2 receptor on the surface of human cells, which triggers the viral membrane to fuse with the host cell membrane, allowing the virus to enter the cell (Monteil et al., 2022). Due to the essentiality of the Spike/ACE2 interaction for viral transmission and survival, most of the current vaccines and therapeutics for SARS-CoV-2 target this interaction (Kyriakidis et al., 2021).
A recombinant human soluble ACE2 (APN01) has previously been described to protect mice from acute lung injury and acute respiratory distress syndrome (ARDS) (Imai et al., 2005), which led to its selection for preclinical and clinical development in lung disease (Haschke et al., 2013; Treml et al., 2010).
Monteil et al. (2021) considered it crucial to assess whether APN01 could indeed bind to the RBD of the Spike protein and the full-length Spike of current SARS-CoV-2 variants, as well as to determine whether the binding of APN01 to the Spike could neutralize SARS-CoV-2 infection. Their study aimed to understand the impact of various single and compound mutations, especially in the RBD of the viral Spike, on the interaction with the ACE2 receptor.
To go about this the researchers systematically tested whether SARS-CoV-2 variants described in the literature and databases affected Spike/ACE2 interactions. They analysed the RBD variants using ELISA analyses to evaluate their binding to ACE2/APN01 and conducted Biacore surface plasmon resonance (SPR) and comparative kinetic binding analyses using the original Wuhan SARS-CoV-2 isolate as a reference. The results revealed that almost all the tested RBDs, including variants of concern (Alpha, Beta, Gamma, Delta and Omicron), showed increased binding affinity to APN01.
Figure 1. Representative SPR sensorgram images for the SARS-CoV-2 RBD/APN01 interaction of current VOCs.
The researchers also assessed the binding of APN01 to full-length pre-fusion Spike proteins by immobilizing the VOC trimeric pre-fusion Spike proteins on a sensor chip and passing APN01 over the chip. They observed strong binding of APN01 to the pre-fusion Spike trimers of all the tested variants, with enhanced apparent affinity and calculated first step affinity for Alpha, Beta, Gamma, and Delta trimeric Spike proteins compared to the reference strain.
The study also preformed neutralisation assays in VeroE6 cells and in human lung epithelial cells to test whether APN01 could neutralise variant clinical SARS-CoV-2 isolates. The inhibitor potency against all the variants was compared to the reference strain. APN01 was found to potently neutralise all the SARS-CoV-2 isolated tested, reducing the viral load of all tested variants present in the cells in a dose-dependent manner. The neutralization potency was also found to closely correlate with Spike/APN01 binding affinity.
Overall, the results from the study by Monteil et al. indicate that clinical grade soluble human ACE2 (APN01) effectively binds to and neutralizes SARS-CoV-2 infections, making it a potentially universally efficacious therapeutic approach to treat current and future variants of SARS-CoV-2, as well as other coronaviruses that require ACE2 to enter host cells. The identification of such a therapeutic could serve as a crucial step in mitigating potential social and economic devastation caused by forthcoming SARS-CoV-2 variants.
References
Harvey, W. T., Carabelli, A. M., Jackson, B., Gupta, R. K., Thomson, E. C., Harrison, E. M., Ludden, C., Reeve, R., Rambaut, A., Peacock, S. J., & Robertson, D. L. (2021). SARS-CoV-2 variants, spike mutations and immune escape. In Nature Reviews Microbiology (Vol. 19, Issue 7, pp. 409–424). Nature Research. https://doi.org/10.1038/s41579-021-00573-0
Haschke, M., Schuster, M., Poglitsch, M., Loibner, H., Salzberg, M., Bruggisser, M., Penninger, J., & Krähenbühl, S. (2013). Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects. Clinical Pharmacokinetics, 52(9), 783–792. https://doi.org/10.1007/s40262-013-0072-7
Imai, Y., Kuba, K., Rao, S., Huan, Y., Guo, F., Guan, B., Yang, P., Sarao, R., Wada, T., Leong-Poi, H., Crackower, M. A., Fukamizu, A., Hui, C. C., Hein, L., Uhlig, S., Slutsky, A. S., Jiang, C., & Penninger, J. M. (2005). Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature, 436(7047), 112–116. https://doi.org/10.1038/nature03712
Kyriakidis, N. C., López–CCortés, A., González, E. V., Grimaldos, A. B., & Prado, E. O. (2021). ortés, A., González, E. V., Grimaldos, A. B., & Prado, E. O. (2021). SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. In npj Vaccines (Vol. 6, Issue 1). Nature Research. https://doi.org/10.1038/s41541-021-00292-w
Monteil, V., Eaton, B., Postnikova, E., Murphy, M., Braunsfeld, B., Crozier, I., Kricek, F., Niederhöfer, J., Schwarzböck, A., Breid, H., Devignot, S., Klingström, J., Thålin, C., Kellner, M. J., Christ, W., Havervall, S., Mereiter, S., Knapp, S., Sanchez Jimenez, A., … Penninger, J. M. (2022). Clinical grade ACE2 as a universal agent to block SARS-CoV -2 variants . EMBO Molecular Medicine, 14(8). https://doi.org/10.15252/emmm.202115230
Pereson, M. J., Flichman, D. M., Martínez, A. P., Baré, P., Garcia, G. H., & Di Lello, F. A. (2021). Evolutionary analysis of SARS-CoV-2 spike protein for its different clades. Journal of Medical Virology, 93(5), 3000–3006. https://doi.org/10.1002/jmv.26834
Treml, B., Neu, N., Kleinsasser, A., Gritsch, C., Finsterwalder, T., Geiger, R., Schuster, M., Janzek, E., Loibner, H., Penninger, J., & Loeckinger, A. (2010). Recombinant angiotensin-converting enzyme 2 improves pulmonary blood flow and oxygenation in lipopolysaccharide-induced lung injury in piglets. Critical Care Medicine, 38(2), 596–601. https://doi.org/10.1097/CCM.0b013e3181c03
When writing this and looking back on this year, I’m realizing that there are a lot more core experiences than I’d have thought. I feel like a reflective piece typically starts off with a few challenges, you add a positive spin, and then end up with a revelation. Well, I’ve had my fair share of challenges this year, but finding the positive spin may have been the hardest.
Entering into this year I wasn’t nervous, I was ready. This was the course I had been looking forward to, dreaming of, since I first learnt about what a neuron was two weeks into first year psychology. I was ready to learn, ready to engage, ready for a challenging year but ready to really push myself. I sat at home over December and imagined staying late in the library reading research papers and going through lectures, learning things that would completely revolutionize the way I thought about things now, and desperately wanting to share what I’ve found out with my family, my friends; since that is what university has been for me. You have no idea how ready I was.
What a year it has been.
The general techniques course definitely catered for a preferred group of science students –students from biochemistry, genetics, and microbiology. Now, coming from a background of human physiology and psychology, I really did get the new learning experiences and late nights in the library I was hoping for, as a lot of the time it felt like I might as well have been in a lecture on engineering. This meant I had to get creative! Having to find a way to “twist” the guidelines/instructions of assignments to steer the learning experience towards something that I could even remotely relate to really did allow me to exercise parts of my brain that I would not have been able to otherwise.
Within the Neuroscience course, a large portion of the coursework was a repeat of what I learnt last year (having come from UCT), which was great as I didn’t really have to learn many new things this year at all. Knowing or being familiar with most of the information allowed me to focus less and was pivotal in driving a decrease in motivation – it made me especially eager to put in much more effort towards all things unrelated to my course.
I also gained a few skills over the course of the year, although, not from the techniques course like we all thought we would (believe it or not, you can only squeeze so much into a 20-minute visit to an MRI machine). Instead, the disorganization taught me how to be flexible when things changed last minute, the patchy communication helped me learn patience, having things in the exams that we weren’t taught helped me learn acceptance, and unconfident responses to queries allowed me to feel comfortable with feeling uncomfortable.
The course also promised a lot of free time, what could be better? And this promise was kept– the lecturers even spoke a mile a minute to make sure they would fit everything into the one-and-a-half-hour slot for that day. I think the purpose of the free time was to engage more with the content ourselves. And some lecturers actually went above and beyond to help with this, by devoting extra time to going and removing the text from the lecture slides before sending them to us, leaving only the beautiful pictures. This did work though, as after spending the lecture frantically trying to take photos of the slides with writing, we went home and spent hours typing it all out again. Looking back, I think this really helped with engaging with the content, and trying to figure out what text matched which picture also turned learning into more of a (laborious) game than a task. But it wasn’t all fun and games. Throughout this year a challenge I’ve faced is trying to reignite that excitement for learning, and I really do pride myself on being able to do that even when the lecturer’s sighs before presenting each slide kept blowing out the match.
Within Neuroscience you were either guided towards wet lab work or neuroimaging. I didn’t fit in either of those. Fortunately, my project – on the perception of sleep – different from the others that were offered, was really what saved this year for me. Even though it was a mammoth task, the interest it sparked in me reminded me of why I enjoyed research and that there are things within the field of neuroscience that are meant for me, even if the course didn’t specifically cater for them.
Overall, I think this year was definitely unexpected, and I think I’ve learnt a lot, made a lot of great friends and core memories. I had to find ways to overcome challenges, get creative when it was called for, and persevere when I really didn’t want to. Would I do it again? I don’t think so. But I am glad I did it, as it taught me where I belong, where I do not, and where I want to be going forward.
Health Science Reviews 