Author: Sachit Swaminathan

 

During your time at Georgia Tech, as a STEM major, one of the things that you might choose to do is to TA a class. TAing a class can be extremely rewarding, despite being a lot of work and it can teach you a lot of concepts that you may not have understood when you took a class. It can also teach you how to communicate your understanding, and the insights that you have taken away/obtained from going through a specific class can also enable you to adapt to new and innovative ways of thinking about and solving a problem, based on the input that you obtain from other individuals. You may or may not TA during your time at Georgia Tech. However, just in case you do, I would like to provide my insight TAing for a core STEM class in my BME curriculum to provide insight into how I felt, what I learned about TA/teacher – student interaction, and how to make the most out of the experience. I am hoping that this inspires more people to become TAs for STEM classes, or just to understand how being a STEM TA is from a former STEM TA’s perspective.

Last year, specifically, I was a TA for an Introduction to Biomedical Engineering Design class. A lot of people have asked me what that experience was like, and what I learned and what kind of growth I experienced as a result, both personally and professionally. Thus, I would like to share some key takeaways and insights that I have gained and how I felt doing this TA job, as someone who had never previously done it before.

I was excited and nervous, as I surveyed the room around me. It was my first day as a BMED 2310 TA in Spring 2023 and a TA, in general, and I had no idea what to expect. I walked into a class full of unknown people, and it only became more daunting as it went from there. It was the first day of class, and everyone was staring at their phones, almost in boredom and a complete lack of interest in being there. We were beginning to do ice-breakers, and everyone was asked to name a fun fact about themselves, and the origins of their name. I was never a person who liked icebreakers. For a long time, I found them pointless, and talking comfortably in front of strangers was not my jam. However, I was here in this situation. I could not just not participate in an icebreaker. So, I told the students my name, and the origin of it, and tried to crack a joke and tell something funny about myself. However, I was just faced with blank stares. I did not know if I was just awkward, or if the students were not interested in what I had to say. Regardless, it was daunting, but I tried not to get discouraged. After all, it was just my first day. Leaving class, I tried to have more hope for the next day, but I was not sure that anything was going to improve.

Walking into class the next day, I tried to be more optimistic. Maybe the kids were just tired. Maybe they did not like the class, or maybe they did not like other classes they were taking this semester. Maybe it had nothing to do with me. So, I went ahead and started explaining the lesson plan for the second day. I explained to them how their lab notebooks should look, and what type of information was expected to be seen in that notebook. I also introduced them to their Fusion Assignment and explained what they should look into, and how they should seek help if they needed it. However, students still looked uninterested and were extremely quiet. Later on in the class, as students were working on their Fusion Assignments, one of them asked me a Fusion-related question. They were having trouble with a certain step involved in the conversion between the 2D schematic and the 3D creation of the structure, and they wanted my advice as to how I could help them. I told them that I unfortunately did not know the answer, as my Fusion skills were rusty, and I needed a refresher on it. I asked the other TA’s if they could help more effectively. The students looked at me in an annoyed manner, and I just felt more out of place. Why had I chosen to TA this class? Why did students think that I was such an ineffective TA if they did? How could I become a better TA? It was then that I thought of trying something else.

I decided that during the next class, I was not going to try to act like a professor or a person of higher authority. Rather, I was going to act more as a friend of the students. I was going to be more open, and try to be more relatable. From then on, during every class, I would ask the students how they were doing, how their semester was going and how their classes that semester were going, and what I could do to help them. From then on, I found that they slowly became more open and began to come out of their shells more. Suddenly, they were much more engaged in class and much more engaged in what I was saying, and I was still not necessarily able to explain everything nor did I know everything. However, things were generally off on a better track.

So, what were my key takeaways from this experience you ask? One of the largest takeaways was that one of the most rewarding parts of being a BME TA is the potential that you get to see, as to what students can innovate and create, and how the ideas that students have shape up into larger prototypes and physical and computational models. Another key takeaway was that BME design classes help prepare students for greater and larger challenges, ahead in industry and in the workplace, and being a TA is important as you can guide students through these experiences and help push them to take on new challenges, and push the envelope on the tasks that they pursue. TAing this class also deepened my understanding of the interdisciplinary nature of concepts, and how they all tie together to ultimately solve problems/issues. For example, when I talked to a group that was doing a Laparscopic surgery project, they told me how the physics of the Laparascopic stapler and the material properties behind the Laparoscopic staples tied into their decisions about how they designed the stapler and what parts they ultimately chose to utilize and what method they used to create it. This was really a eureka moment for me because I had done a project on improving Laprascopic surgery, but I had only looked at it from the vantage point of Biology and Biomedical Engineering. I had not done deep introspection into how multiple concepts could tie into the success of this Laparoscopic stapler. This was widely insightful for me, and it really got me to consider how multiple areas of science could converge and intersect to ultimately solve poorly-defined, and complicated problems.

Part of the reward of being a Biomedical Engineer is the opportunity to explore fascinating and cutting-edge work that teaches me new skills and exposes me to unique challenges every semester. Throughout my journey, I’ve learned coding, worked with circuits, conducted detailed statistical analyses, and performed rigorous statistical tests. However, this semester, I had the chance to do something I had never experienced before. I worked with cancer cells. Yes, you read that right! I worked with cancer cells in a wet lab environment!

What is a wet lab, you ask? It’s a controlled environment where you work with potentially hazardous cell cultures and substances while following strict safety protocols, such as wearing gloves, goggles, lab coats, and disinfecting surfaces with ethanol to avoid contamination. Mistakes can introduce bacteria or other pathogens that could destroy your cultures, making careful adherence to procedure critical. Despite the challenges, working in a wet lab is an incredibly rewarding experience that not everyone gets to have. To share this unique experience, I want to provide some insight into what a typical experiment looks like in a wet lab, so those who haven’t had the opportunity can get a feel for it. Trust me, you’ll find it fascinating!

One of the experiments I conducted this semester involved treating Glioblastoma (U87-EGFP) cells with varying concentrations of Nickel Sulfate (NiSO₄) to assess its effects on cell viability. Intuitively, I hypothesized that increasing concentrations of Nickel Sulfate would be progressively toxic to these cells. Sure enough, that’s exactly what happened. The coolest part? I didn’t even need to run complex calculations to see the effects! By observing the cells under a microscope, I could identify the toxicity based on changes in cell morphology and network structure. Let me explain how this works.

When cancer cells are healthy, they exhibit a spherical shape and form densely interconnected networks, similar to what we see in normal, healthy cells. However, as cells are damaged, these networks weaken, and their shapes become less defined and less spherical. These morphological changes occur because interactions between the cells’ mitochondria and cytoskeleton are disrupted. Observing these changes during the experiment allowed me to visually interpret the effects of Nickel Sulfate on the cells. Below, I’ve described and analyzed the experiment’s results to demonstrate how the process unfolded in real time.

Figure 1A. Appearance of U87 – EGFP cells, after addition of 0 mM of NiSO4. Cells appear to be healthy, as they are exhibiting a bright color, are elongated in shape, and are forming an interconnected network like structure.

Figure 1B. Appearance of U87 – EGFP cells, after addition of 0.0625 mM of NiSO4. Cells still appear to behealthy, but they are slightly less elongated, and are slightly less bright in color, as compared to when 0 mM ofNiSO4 was added. The cells do still appear to be interconnected, though.

Figure 1C. Appearance of U87 – EGFP cells, after addition of 0.125 mM of NiSO4. Cells appear to be less healthy, and are significantly less elongated and bright, compared to when 0 or 0.0625 mM of NiSO4 wasadded. Cells also appear to be significantly less interconnected, as the network structure is weakening. The addition of NiSO4 at this concentration seems to be having a significant impact on the structure of NiSO4, indicating that the IC50 concentration is being approached.

Figure 1D. Appearance of U87 – EGFP cells, after addition of 0.25 mM of NiSO4. Cells appear to be significantly less healthy, and there is hardly any presence of elongation, compared to when 0, 0.0625, or even0.125 mM of NiSO4 was added. There also appears to be hardly any network structure left between the cells, as all interconnections are not visible. The cells are also significantly less bright, and are extremely dim. The significant structural changes that arise from the addition of this concentration of NiSO4 indicate that the IC50 concentration has been passed.

Figure 1E. Appearance of U87 – EGFP cells, after addition of 0.50 mM of NiSO4. Cells appear to be significantly less healthy, and do not have any visible interconnected network structure. Any slight presence of anetwork structure seen when 0.25 mM of NiSO4 was added also appears to be gone. Now, there appears to be no network structure.

Figure 1F. Appearance of U87 – EGFP cells, after addition of 1 mM of NiSO4. Cells appear to be significantly less healthy, as there is no elongation present. There is also no network structure left between the cells. No interconnections appear to be visible. The cells are in a completely opposite state to how they were, from a color perspective, when they were treated with no NiSO4. Given the permanent changes in structure and morphology of the cells, it is likely that the addition of 1 mM NiSO4 has the maximum possible impact on the cells. In other words, it is likely adding any more NiSO4 will have a marginal impact, if any.

Overall, observing these morphological changes was an eye-opening experience for me as it taught me to analyze cellular changes, in a relatively simple way, without relying on quantiative measurements or complicated formulas, something that I never knew that you could do as an Engineer! It also taught me that cancer is not as invincible as it is made out to be and it can indeed be quashed. This is something that I never knew until I did this experiment, and it gave me a lot of hope for the future of cancer treatment!

Reading this post, I hope you got inspiration to work in a Wet lab too one day as you see all the cool stuff that you can do/accomplish. Sometimes, you do not have to be a fancy scientist at the NIH or the CDC to make a difference. Occasionally, just the Georgia Tech student can accomplish some pretty cool stuff!

 

 

If you have ever entered into a STEM major at Georgia Tech, or at any other school, you know that it is not easy business. Sleepless nights, tears, wanting to rip your hair out (It’s an expression don’t worry!) are all parts of the package. You end up learning a lot of useful information for your future career, and for your personal life that you will definitely utilize to achieve your goals. Nevertheless, along the way, there are plenty of times that you will doubt yourself and your capability to survive your major. Being a Biomedical Engineering major, a major that combines elements of pre-med, and Engineering, I know first hand how this feels. I have had more challenging classes throughout this major than I can count from Conservation Principles of BME, to Intro to MATLAB, to Organic Chemistry I, to Organic Chemistry II, to Statics, to Biotransport, to Systems Modeling this semester. It is constant stress, and hardwork! It is rewarding hardwork, but it is hardwork nonetheless. One of the things that helped me every semester when I felt overwhelmed through this workload was to know that other people were also going through what I was going through, and were as stressed out as I was. So, being a fifth year BME and STEM student at Georgia Tech, I wanted to write this article to provide solace to people who felt overwhelmed, so they feel like there are people who have gone through what they have gone through and that they are not alone in the challenges that they face. So sit back and relax, as I take you through my journey as a STEM student taking Biomechanics and the hurdles and misery I felt as I went through the class.

To start off, throughout high school and most of my life, I was good at math and science. Others looked at subjects like AP Chemistry with dread, while those subjects gave me joy. After all, there was nothing more fun than working on Stoichiometry problems on a Friday night, right? Others would walk into Chemistry class, with a look of dread on their face, while I would walk in with a feeling of excitement. Making solutions in the lab was my jam. We would have quizzes every Friday, and I could see the feeling of dread on my peers’ faces afterward as they turned in their papers with half-empty work, not confident that they had solved the problem correctly, while I had solved the problem confidently from start to finish. I was riding a sugar high, and it felt great to be at the top. There was a great feeling that came with feeling so confident about science and I really enjoyed what I was learning as well. Unfortunately, little did I know that this was just a positive moment, and that, in the grand scheme of things, I was in for a tough reality.

Fast forward to my senior year of college. I had registered to take Biomechanics. It was a course that was required for my major. I had heard awful things from some of my friends who had taken it before me, but I went in with an open mind. The first few lectures went by, and I already felt slightly confused, but I had been able to clarify concepts that I was struggling with. I was able to do the practice problems. Nothing seemed too concerning.  Then came the day of the quiz on Wednesday. Most people had not done the practice problems, and I was feeling ready. It was approaching the last 25 minutes of the lecture, and the professor and TA’s began handing out the papers. I knew it was not going to be easy, but I felt prepared, or so I thought.

I flipped the paper over, only to see a diagram with a lot of text that I could not comprehend. I tried to calm myself down and reread, but I just could not understand. It was then that I saw the time on the screen going down, 20 minutes, 19:59, 19:58, 19:57. With each passing second that went by, I was losing time, and I was still not able to understand the question prompt or the way my Free Body Diagram should look. With each second that went, I could feel a ticking time bomb going off in my head. My stomach began to burn like lava. My chest began to feel constricted, and I felt like I could not breathe. To make matters worse, I heard the sounds of chairs moving in and out beside me, as people began to turn in their quizzes and leave. People were writing so loudly that it almost made the desks shake, and it just made me feel even more nervous than I already was. In the last 10 minutes, I wrote down some work and formulas, hoping to get some credit. However, I did not get a good feeling about how this was going to go, and my gut feeling was usually correct. Seeing as my approach to studying for this quiz had probably failed, I decided to modify my studying approach for the next quiz, next Friday.

Unfortunately, modifying my approach did not change the outcome of the next quiz. The next quiz also felt just as impossible, and now that it had been two quizzes like this, I began to think I was just screwed in this class, no matter what I did. I then went home, tired, and not aware of what to do. I took a break from Biomechanics because, after all, I was going to suck no matter what, right? The grade for the first quiz came that Sunday, and it was even worse than I could have ever expected. I had gotten a 0. It seems I had managed to not even get any partial credit. As dramatic as this sounds, I then began to contemplate all my life decisions, including coming out of state to Georgia Tech to study BME. Maybe I was just not cut out for it? I had already spent many semesters before this, feeling dumb about struggling in classes at Tech, having a lower GPA than some others, and not getting a single internship until the summer after my junior year. In truth, I was doing fine, but I still doubted myself because BME was a hard major. Any Engineering was a hard major, and there were plenty of people that had quit before me and that had not even made it nearly as far as I had made it. It is extremely common, unfortunately, for people in STEM majors to drop out and some classes make many people more tempted to drop out than to stick it through.

In the second half of the class, I began to make up ground. I began to get 80’s and 90’s on the quizzes, and I even got a 98 on the second test. I had not changed much at all about the way I studied, except I had become calmer, as I had decided that the worst thing that would happen was that I would fail. I was not prepared to drop the class, in the rare chance that I passed. I finally finished the class, and it was still not my best grade, but I ended up with a way better outcome than I thought I was going to end up with in the beginning. I persevered, and that is when I realized that I was good at self-learning, even if I did not think so initially. I was proud of myself, and I felt a sense of joy as to what I was able to accomplish. So, I just want to say, for anyone coming from a STEM background who feels intimidated and hopeless about being successful in your major, you will encounter difficult times and difficult situations. However, if you are motivated to push through and persevere, you can not only find success, but you can enjoy your major while going through the challenge.

Antibiotic resistance has increased global deaths by 8% between 1990 and 2021 and is expected to be a leading cause of death by 2050 [1]. Based on projections, 11.1 million deaths due to Antimicrobial Resistance could be prevented if a treatment is devised to effectively inhibit Gram-negative B – Lactam bacteria that have undergone these mutations [1]. However, the lack of an effective antibiotic treatment is causing β– Lactam antibiotic resistance to be an unnecessary top cause of disease burden/death. This is why it is imperative to get down to the molecular mechanisms behind antibiotic resistance, so something can be done about this catastrophe. Now, I know I am just a Georgia Tech student. However, I hope to shed some light on this issue today, so I can communicate to the general public and to the non-scientists out there that this really is a solvable problem. It really is not as dire as it seems. So, sit back and relax, as I take you through a journey, looking into the history of β-Lactam Antibiotics, β-Lactam Antibiotic resistance, and mutations that have occurred that have allowed Gram-negative bacteria to become so powerful and what we as people can do about this!

β-Lactam Antibiotics, such as penicillin, have been used to treat a wide variety of bacterial infections due to the diversity of mechanisms with which they can work, such as their ability to promote the breakdown of the peptidoglycan layer of the cell wall via the targeting of binding proteins, transport proteins that transport peptidoglycan precursors across the cell wall, phospholipids that normally decrease permeability, etc [2]. Recently, however, the overreliance on β-Lactam Antibiotics has led to the development of resistance mechanisms in β-Lactam bacteria to counteract the effects of these antibiotics, the main one being the evolution of β-Lactamase enzymes [4]. This is due to evolutionary and selective pressure, which cause Gram-negative bacteria to develop resistance mechanisms to evade the effects of antibiotic treatment, especially though the development of mutations in their lactamase enzymes [4,5]. Resistance mechanisms in β-Lactam bacteria take the form of Standard beta-lactamase (SBL) and extended spectrum beta-lactamase (ESBL) mutations.

The two mutations differ primarily in their substrate specificity and the complexity of their mutations. SBL mutations enable SBLs to hydrolyze first-generation β-Lactam Antibiotics, whereas they fail to effectively enable hydrolysis of second or third-generation beta-lactamases [6, 7]. On the other hand, β-Lactam bacteria, with more complex mutations that help to increase the number of substrate– binding sites and the size of the active site, allow for the hydrolysis of a broader and more diverse range of antibiotics, increasing catalytic efficiency and conformational flexibility [7]. The result is more formidable antibiotic resistance, which poses a significantly greater threat compared to standard mutations [8]. Examples of β-Lactamase enzymes with these ESBL mutations are the TEM, KPC, and CTX-M enzymes. The danger with these mutations is that they spread easily through plasmids, which replicate independently of an organism’s chromosomal DNA and can transfer genes to other bacterial cells via horizontal gene transfer [9]. This means that mutations conferring resistance can quickly spread to multiple bacterial cells making it very difficult for antibiotic treatment to be successful [9,10]. Based on projections, 11.1 million deaths due to Antimicrobial Resistance could be prevented if a treatment is devised to effectively inhibit Gram-negative B – Lactam bacteria that have undergone these mutations [1]. This makes it imperative to better understand the molecular mechanisms behind what makes these Amino Acid mutations so advantageous in the TEM, KPC, and CTX-M enzymes so that more effective treatments to tackle antibiotic resistance can be devised. This paper focuses on the molecular mechanisms behind such mutations that enable Gram-negative bacteria to better bind to the side chains of extended-spectrum β-Lactam Antibiotics to help achieve that goal.

As alluded to earlier, mutations in Gram-negative bacterial proteins leading to resistance began with standard spectrum β-lactamase (SBL) mutations (S70 → S70G, E166 → E166N, K73 → K73H). The S70G mutation enabled β-lactamase enzymes to conduct a nucleophilic attack on the β-lactam ring, while the E166N and K73H mutations helped stabilize the transition state of this reaction with the side chains of β-lactam antibiotics, such as penicillin [11]. However, at this point, the worst-case scenario had not yet materialized because the active site of the β-lactamase enzymes could not accommodate extended-spectrum β-lactam antibiotics with bulky oxyimino side chains at the C7 position. These side chains were too large, and the active sites lacked the conformational flexibility to accommodate them [11]. The binding affinity (Km) was too high, and catalytic efficiency was too low for hydrolysis to occur. Extended-spectrum β-lactamase (ESBL) mutations, however, overcame this limitation by enhancing the ability of the bacteria to bind extended-spectrum β-lactam side chains. ESBL mutations, such as G238S, R164S, and E104K, expanded the active site through structural changes in the omega loop, allowing for new interactions between the enzyme and side chains, such as electrostatic interactions and hydrogen bonding [11, 12]. This significantly increased catalytic efficiency and decreased Km. Various gain-of-function mutations enabled β-lactamases to degrade β-lactam side chains more effectively, increasing the likelihood of significant antibiotic resistance [12].

For example, the G238S and R164S mutations in TEM enhance degradation by significantly increasing the conformational flexibility of the β-lactamase active site, by promoting the formation of Hydrogen bonding networks, allowing for the effective accommodation of the bulky R1 and R2 side chains of second-generation βlactam antibiotics, such as cefotaxime and ceftazidime [12]. This increased flexibility improves the binding affinity between the active site and the side chains, thereby increasing the acylation rate of cefotaxime and ceftazidime [12, 13]. As a result, catalytic efficiency and turnover rate also increase. Other mutations, such as E104K and E240K, further increase catalytic efficiency by enhancing electrostatic interactions between the β-lactamase active site and the β-lactam side chains, thus reducing aggregation and promoting proper folding [13, 14]. This phenomenon of enhanced hydrolysis due to increased flexibility is also seen in KPC β-lactamase, where the V240G and H274Y mutations improve the accommodation of the ceftazidime side chain by increasing the conformational flexibility of the β3 strand and introducing a tyrosine residue that participates in pi-stacking interactions with positively charged residues on the β-lactam side chain, further increasing catalytic turnover and facilitating hydrolysis [15].

Some mutations enhance the hydrolysis of β-lactam side chains by stabilizing the β-lactamase enzyme, enabling it to withstand other mutations that could otherwise destabilize it. For example, the M182T mutation introduces a polar side chain with a hydroxyl group, which can participate in hydrogen bond network formation [16]. This helps compensate for destabilizing effects caused by mutations such as G238S and E104K, by promoting correct protein folding and reducing the likelihood of significant aggregation [16]. Similarly, the A237T mutation introduces a polar side chain that facilitates hydrogen bonding and dipole–dipole interactions [16, 17]. In metalloβ-lactamases, such as New Delhi Metallo-β-Lactamase (NDM-1) and Verona-integron encoded metallo-βlactamase 2 (VIM-2), mutations like D124N, H189Y, H120R, and H263Y can enhance metal ion coordination within the active site, such as zinc binding, thus increasing overall enzyme stability and activity. These stabilizing mutations can offset the negative effects of destabilizing mutations, such as R244S, which weakens enzyme stability by disrupting ionic and hydrogen bond networks with the introduction of smaller polar side chains, and S130G in TEM-1 β-lactamase, which disrupts protein folding by affecting hydrophobic interactions in the core, breaking hydrogen bonding networks, and impairing the stabilization of enzyme loop regions due to the loss of a polar group after mutation [18, 19].

Finally, other mutations enhance the hydrolysis and degradation process by promoting the formation of new bonds, bond networks, and intermolecular forces between residues in the β-lactamase enzyme active site and the β-lactam side chains. Initially, wild-type CTX-M β-lactamase enzymes were ineffective at hydrolyzing the βlactam side chains of certain β-lactam antibiotics, such as ceftazidime, because the predominant mutations only allowed for the accommodation of smaller β-lactam side chains, such as those found on cefotaxime [11]. However, mutations that wild-type CTX-M β-lactamase enzymes later underwent, such as D240G and P167S, enhanced the fit of the aminothiazole ring of ceftazidime into the β-lactamase active site and altered the steric conformation of proline from cis to trans, respectively, allowing for the formation of electrostatic interactions and new hydrogen bonds with the β-lactam side chains [11, 20]. This occurs because Proline has an extremely rigid cyclic structure, so by mutating to Serine, its flexibility increases, enabling it to form more bonds. This ultimately increases catalytic efficiency and enhances hydrolysis [21].

Overall, these results suggest that key mutations, such as R164S & G238S in TEM, P167S & D240G in CTX-M, etc. work to induce resistance to β-lactam antibiotics, by promoting increased conformational flexibility, increasing the stabilization of the β-lactamase enzyme, and enabling the formation of new bonds between the active site residues on the enzyme, and the side chains of the antibiotics. The questions that remain are how these mutations can ultimately induce multi-drug resistance, either to different classes of antibiotics or different types of β-lactam bacteria, and what methods can be harnessed to specifically target β – Lactamase enzymes and slow down the rate at which they undergo mutations.

References

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20. Turner J, Muraoka A, Bedenbaugh M, Childress B, Pernot L, Wiencek M, Peterson YK. The chemical relationship among beta-lactam antibiotics and potential impacts on reactivity and decomposition. Front Microbiol. 2022; 13: 807955.

21. Kim D, Kim S, Kwon Y, Kim Y, Park H, Kwak K, Lee H, Lee JH, Jang KM, Kim D, Lee SH, Kang LW. Structural insights for β-lactam antibiotics. Biomol Ther. 2023; 31(2): 141–147.

Neural Tube Defects (NTDs) are a type of birth defect that can impact the brain, spine, or spinal cord during the early stages of fetal development (1). Common NTDs that fetuses develop include Spina Bifida, Anencephaly, Encephalocele, and Iniencephaly (5,6). NTDs have a strong global prevalence, impacting approximately 322,000 pregnancies worldwide annually (2). In the United States alone, NTDs occur in approximately 3,000 babies annually, with 1,000 of those affected experiencing Anencephaly (1,3,4). NTDs are particularly challenging to treat early, with no effective treatments, as the defects typically begin developing during the first month of pregnancy, which is when some women may not even know they are pregnant (1). Unfortunately, by the time Neural Tube Defects are correctly and definitively diagnosed, it becomes extremely difficult to effectively treat it. Prior to researching more, I had never heard of Neural Tube Defects! However, being a Biomedical Engineer, I only felt that it was my role and responsibility to contribute at least a little bit of the principles that I have learned to come up with new therapies! Who knows? Maybe, it can help someone one day. So, in this article, I decided to highlight what genes I thought of targeting so far. While this may turn out to be a nothing burger, hopefully it’s at least an interesting read for you all!

Previous literature that I read through established the FOX1, ANKDR6, and WDR4 genes as significant contributors to the development of neural tube defects. Based on this, I came up with two methods by which normal functioning of these genes can be restored, and NTD development can be prevented, both carried out before the 6th week of the first trimester of pregnancy, since that is when the neural tube closes. Each of the genes being targeted plays a significant role in normal transcription regulation/signaling mechanisms that, when disrupted, lead to NTD’s. ANKDR6 mutations affect normal reciprocal mechanisms, causing motor neuron pools to be deactivated, hindering muscle innervation (7). WDR34 mutations affect the PCP signaling pathway, impacting muscle regeneration and neuron orientation (9,10,11); 3). FOX1 gene mutations lead to the formation of abnormal FOX1 proteins, which affects downstream transcriptional regulation of NTF mechanisms (8,12). The rationale for having two methods is that a comparison of both the methods will provide insight into which one is more effective in preventing NTDs over the long-term, especially given the known limitations of synthetic oligonucleotides for gene editing and removal. These aims will be tested on pregnant mice, whose fetuses have mutations in these three genes. 

As you can see below, based on the research that I did, I compiled a few more details for each of my aims. These are works in progress, but using my creative mind, this is what I was able to think of!

Aim 1: Utilize synthetic oligonucleotides with Homology Directed Repair to edit genetic mutations in the FOX1, ANKDR6, and WDR4 genes to prevent the formation of Neural Tube Defects.

1. Mice will be randomly assigned to treatment, placebo, and control groups. 
2. For the treatment group, complementary DNA Oligonucleotides to the genes will be created, while those unrelated to the three genes will be created for the control group and none will be created for the placebo group (13).
3. Synthesize Repair DNA template strands, with Fluorescent Reporter Genes (GFP, BFP, MCherry), using promoters. They will then be ligated/joined with the oligonucleotides (14,20,21).
4. The oligonucleotides with the fluorescent reporter genes will be successfully delivered to the somatic cells of the fetuses, through lipid nanoparticles (18,19). This will facilitate a double strand break at the ends of each of the three genes, which will promote their deletion, due to the HDR Mechanisms present in the cell (15,16,17).
5. After enough time has passed, these cells will be harvested, and inserted through a flow cytometer. MFI will be measured, with a higher MFI, correlating to a higher success of gene removal (23).

Aim 2: Utilize Crispr-Cas9, with HDR via a Lipid Nanoparticle delivery system to edit genetic mutations in the FOX1, ANKDR6, and WDR4 genes to prevent the formation of Neural Tube Defects.

1. Mice will be randomly assigned to treatment and control groups.
2. For the treatment group, guide RNA strands that correspond to the three genes will be created, while nonspecific guide RNA strands will be created for the control group (16).
3. Synthesize Repair DNA template strands, with GFP, BFP, MCherry, using promoters (14). The Cas9 proteins, the gRNA and the repair template DNA will be delivered, through lipid nanoparticles (18), to the somatic cells of the fetuses. This will facilitate the breakage of the strands containing these genes, and their substitution with strands that lack these genes and express proteins that induce fluorescence (15,16,17). 
4. After enough time has passed, these cells will be harvested, and inserted through a flow cytometer. Mean fluorescence intensity will be measured, with a higher MFI, correlating to a higher success of gene removal.

My hope is that my approach of editing mutated versions of these genes in fetus somatic cells and replacing them, can inspire some scientists to pursue this further, and help to prevent NTD development and save lives. The problem is that, right now at least, if the genes were not edited or replaced, children would inevitably not survive the pregnancy, due to the lack of any effective treatments. These types of diseases simply do not have effective cures, and they require out of the box thinking to make any progress. Conventional wisdom does not always work in science! There are limitations, and challenges down the road, however. Edits will not automatically be passed on to future generations, since they do not affect the germline cells, which means that the offspring of someone who has this gene in their genome will unfortunately still suffer the consequences (19). This is a problem that I unfortunately could not find a way to get around in my methods, but hopefully I have provided a good starting point for other researchers to look into! If you made it this far, kudos to you and hopefully this inspires you to look into these horrible diseases as well!

Sources:

1. Cleveland Clinic Medical Professional. Neural tube defects (NTDs): What They Are, Causes & Prevention. Cleveland Clinic. March 30, 2022. Accessed October 28, 2023. https://my.clevelandclinic.org/health/diseases/22656-neural-tube-defects-ntd. 
2. Kancherla V. Neural tube defects: a review of global prevalence, causes, and primary prevention. Child’s Nervous System. 2023/07/01 2023;39(7):1703-1710. doi:10.1007/s00381-023-05910-7
3. Neural Tube Defects. March of Dimes. February 2022. Accessed October 28, 2023. https://www.marchofdimes.org/find-support/topics/planning-baby/neural-tube-defects#:~:text=Screening%20tests%20for%20NTDs%20include,to%2022%20weeks%20of%20pregnancy. 
4. MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 Jun 24]. Anencephaly; [updated 2019 Oct 01; reviewed 2018 Jun 01; cited 2023 Oct 29]; [about 5 p.]. Available from: https://medlineplus.gov/genetics/condition/anencephaly/. 
5. King, Jesse, “Anencephaly”. Embryo Project Encyclopedia ( 2013-02-13 ). ISSN: 1940-5030 https://hdl.handle.net/10776/4215
6. Amorosi S, D’Armiento M, Calcagno G, et al. FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic Nude/SCID fetus. Clinical Genetics. 2008;73(4):380-384. doi:https://doi.org/10.1111/j.1399-0004.2008.00977.x
7. Rai S, Leydier L, Sharma S, Katwala J, Sahu A. A quest for genetic causes underlying signaling pathways associated with neural tube defects. Review. Frontiers in Pediatrics. 2023-May-22 2023;11 doi:10.3389/fped.2023.1126209 
8. Greene NDE, Stanier P, Copp AJ. Genetics of human neural tube defects. Human Molecular Genetics. 2009;18(R2). doi:10.1093/hmg/ddp347 
9. Wu G, Huang X, Hua Y, Mu D. Roles of planar cell polarity pathways in the development of neutral tube defects. Journal of Biomedical Science. 2011;18(1). doi:10.1186/1423-0127-18-66 
10. Butler MT, Wallingford JB. Planar cell polarity in development and disease. Nature Reviews Molecular Cell Biology. 2017;18(6):375-388. doi:10.1038/nrm.2017.11 
11. Hou P-S, hAilín D, Vogel T, Hanashima C. Transcription and beyond: Delineating Foxg1 function in cortical development and disorders. Frontiers in Cellular Neuroscience. 2020;14. doi:10.3389/fncel.2020.00035 
12. Wong L-C, Singh S, Wang H-P, Hsu C-J, Hu S-C, Lee W-T. Foxg1-related syndrome: From clinical to molecular genetics and pathogenic mechanisms. International Journal of Molecular Sciences. 2019;20(17):4176. doi:10.3390/ijms20174176 
13. Sauer NJ, Mozoruk J, Miller RB, et al. Oligonucleotide‐directed mutagenesis for precision gene editing. Plant Biotechnology Journal. 2015;14(2):496-502. doi:10.1111/pbi.12496 
14. Li S, Chen L, Peng X, et al. Overview of the reporter genes and reporter Mouse Models. Animal Models and Experimental Medicine. 2018;1(1):29-35. doi:10.1002/ame2.12008 
15. Smirnikhina SA, Zaynitdinova MI, Sergeeva VA, Lavrov AV. Improving homology-directed repair in genome editing experiments by influencing the cell cycle. International Journal of Molecular Sciences. 2022;23(11):5992. doi:10.3390/ijms23115992 
16. Nambiar TS, Billon P, Diedenhofen G, et al. Stimulation of CRISPR-mediated homology-directed repair by an engineered rad18 variant. Nature Communications. 2019;10(1). doi:10.1038/s41467-019-11105-z 
17. Chen J, Li S, He Y, Li J, Xia L. An update on precision genome editing by homology-directed repair in plants. Plant Physiology. 2022;188(4):1780-1794. doi:10.1093/plphys/kiac037 
18. Givens BE, Naguib YW, Geary SM, Devor EJ, Salem AK. Nanoparticle-based delivery of CRISPR/Cas9 genome-editing therapeutics. The AAPS Journal. 2018;20(6). doi:10.1208/s12248-018-0267-9 
19. Han JP, Kim M, Choi BS, et al. In vivo delivery of CRISPR-Cas9 using lipid nanoparticles enables antithrombin gene editing for sustainable hemophilia A and B therapy. Science Advances. 2022;8(3). doi:10.1126/sciadv.abj6901 
20. Falzarano MS, Passarelli C, Ferlini A. Nanoparticle delivery of antisense oligonucleotides and their application in the exon skipping strategy for Duchenne muscular dystrophy. Nucleic Acid Therapeutics. 2014;24(1):87-100. doi:10.1089/nat.2013.0450 
21. Moss KH, Popova P, Hadrup SR, Astakhova K, Taskova M. Lipid nanoparticles for delivery of therapeutic RNA oligonucleotides. Molecular Pharmaceutics. 2019;16(6):2265-2277. doi:10.1021/acs.molpharmaceut.8b01290 
22. Blackburn L, Brigden T, Hall A, Johnson E. Somatic genome editing: An overview. PHG Foundation. 2019. Accessed November 18, 2023. https://www.phgfoundation.org/briefing/somatic-genome-editing-overview.
23. Bahreyni-Toossi MT, Dayyani M, Mahmoudi M, Azimian H. Flow cytometric assessment of DNA double-strand break and repair kinetics in prediction of intrinsic radiosensitivity. Iran J Basic Med Sci. 2022;25(9):1104-1109. doi:10.22038/IJBMS.2022.65178.14350

Continuing from the previous post, I want to highlight more raps that I have been creating to teach students basic science related topics. In this post, I specifically want to discuss and share Biology-related raps that I have created. While I do not have access to the actual audio files of the raps because they are on my home computer, I can still share the lyrics to hopefully show you how I have been going about this! It all started when I got an email from a past high school teacher of mine asking me if I wanted to become an AP Biology Tutor. At first, I hesitated because it had been so long since I had taken AP Biology or any other Biology course. I was not sure that I remembered enough to teach someone else. The last thing I wanted to do was be a terrible tutor. However, I decided to be courageous and give it a try. Unfortunately, my first two tutoring sessions that I did over Teams were not what I had hoped for. Well, I had thought I explained well, it was clear that the person I was tutoring had not properly understood the concept. After some self-reflection, I decided I needed to try a different approach. That’s when I thought about making a rap song to teach this student the material. We were specifically focusing on the concept of DNA replication in this session. So, I made a rap about DNA replication. Here are the lyrics I’ve written so far:

In the nucleus where the code exists.

We got a lit double helix twist.

This beat gonna slip harder than Sierra Mist.

DNA replication, so many steps, need to make a list.

Enzymes come in; Helicase unwound.

Bonds broken; bonds rewound.

Strands separate, a zipper out in the light.

Replication fork shining real bright.

Primase creates the primer, a starting point.

New DNA strands made, together joint.

Leading strand, continuous traction.

Lagging strand, complete distraction.

Okazaki fragments created, connected like pieces of a puzzle.

Stay calm, no need to get confuzzled.

Proofread code, check for mistakes

Get the Exonuclease crew. That’s a real hot take.

Do the Mismatch Repair. Somethin you’ll really preciate.

I was delighted by what the student told me about their understanding of DNA replication after this rap. Not only did they understand the workflow of the topic better, but they also understood how the different pieces and aspects of the topic came together, even if one aspect only influenced another aspect indirectly. The presence of a higher-level understanding of the topic really heartened me, and it has only corroborated my suspicion that people learn things much better when they are engaged. While only time will tell, if you are teacher or a professor at Georgia Tech or other colleges and you are reading this and you feel like your students are struggling to grasp a concept, feel free to give something like this a try. You might find that you have a lot of fun, and that your students are much less confused! If you do try it, let me know how it goes!

 

 

 

Do you remember the days of 2020? Do you remember the uncertainty, the anxiety, and the constantly changing advice? Do you remember waking up every day, checking the news hoping for something better, but just seeing bad news after bad news? Perhaps, one of the most disheartening aspects of it was the expectations of scientists vs. what actually happened. At every turn, the virus proved more mysterious, complex, and unpredictable than what was anticipated. Every time, we thought that it was over and that we could declare mission accomplished, there was always something unexpected waiting for us. Taking a look back at some of these different moments during the Pandemic, my hope is to depict how the virus surprised us at every turn, and the lessons that we can take away for the next major Infectious Disease Outbreak.

The first surprise that the virus threw at us was that the majority of us believed that our vaccines produced something known as sterilizing immunity. This was the ideal scenario because it meant that not only did the vaccine reduce the incidence of symptomatic and severe disease. However, it also reduced the incidence of infection and how frequently it was transmitted. This meant that, even if someone could not or chose not to get vaccinated, they would effectively be protected because the people around them could not spread the infection. This would decrease the overall community burden of Covid, along with the number of hospitalizations and deaths. Initially, it seemed like our vaccines had the potential to do this. For instance, there were studies in early 2021 showing that “The Pfizer vaccine reduced asymptomatic cases by 89.4%, and symptomatic cases by 93.7%”(Israeli Studies find Pfizer Covid-19 Vaccine reduces transmission). Similarly, many Israeli studies in the early part of 2021 observed the phenomenon that “Vaccines reduced the viral load in the respiratory tract of infected individuals, compared to unvaccinated people who were infected”(Israeli Studies find Pfizer Covid-19 Vaccine reduces transmission). Additionally, as Israel and the United States begun vaccinating their population, cases dramatically decreased. For instance, from January to May, Covid cases in Israel decreased from “1000 million per day to less than 3 per million”(What pushed Israel out of herd immunity? Modeling Covid-19 Spread of Delta and Waning Immunity). Unfortunately, these early signs of optimism were misplaced, and it clouded our judgement and took our eyes off the ball for the challenges that were about to come next.

Around the same time that the incidence of Covid was decreasing in first world countries like the US, Israel, and the UK, the situation was extremely dire in India. In India, the number of infections were significantly increasing, along with the number of hospitalizations and deaths. The cause was not known yet, at the time. However, in April 2021 in India, “56-65-year-olds were spending an average of 13 days in the hospital”(Covid-19 Mortality in the Delta Wave in India: A Hospital-Based Study from Ramanagara District, Karnataka). Additionally, “77-84.62% of individuals in hospitals were completely out of breath, and WBC count was significantly elevated in over 40% of cases”(Covid-19 Mortality in the Delta Wave in India: A Hospital-Based Study from Ramanagara District, Karnataka).  In other words, there were early indications that there was something going on in India that was causing the pathogenicity of Covid to increase, and a significant number of people to get Covid to become seriously ill. To some extent, it was even more than what was seen during the initial Covid wave in New York or during the 2020 winter Covid wave in the United States. This was corroborated by the number of individuals “…needing significant levels of Oxygen”(Covid-19 Mortality in the Delta Wave in India: A Hospital-Based Study from Ramanagara District, Karnataka). Perhaps the largest red flag and warning sign in this situation should have been the fact that most of the population in India had already been infected, and supposedly developed immunity. According to some studies, “55% of India’s population may have been infected by January 2021″(India says it contains spread of COVID-19, no new cases in fifth of country). This only further proves that a new, pathogenic variant that was clearly immune-evasive, and especially adept at penetrating immunity induced by natural infection had arisen and would prove a significant threat to the United States, where so many people had still not been vaccinated. Indeed, the story of what happened in India repeated almost exactly in the United States 2-3 months later.

So, America experienced the catastrophic effects of the Delta variant surge and then believed that everything was over. Surely there was enough immunity in America, so everything would be okay now, right? Unfortunately, the virus was still not done with us. Not only did our cases end up at a higher baseline than they were prior to the Delta surge. However, we then had a new variant arise in South Africa, which was good at evading all the immunity obtained from the Delta Variant, and previous variants. Specifically, “The reinfection rate of individuals who had been infected by other variants was up to 56% according to studies done by Qatar”(Protection against the Omicron Variant from Previous SARS-CoV-2 Infection). On the bright side, there were some positives on the horizon, though. The variant seemed to induce clinically milder symptoms and may have carried a lower risk of Long Covid. The variant also seemed to confer stronger protection to previous variants, suggesting that it was favored to be the dominant variant. For instance, studies showed that after having the Delta Variant, “Many individuals had a 6-fold increase in neutralization ability/capacity”(Omicron infection enhances Delta antibody immunity in vaccinated persons). This was unique to the Omicron variant, as other variants did not appear to provide such a broad immune response, especially to variants that were so dissimilar to it. This raised the hope that Omicron could signal a start to a more stable state with Covid because Omicron would be able to block reinfection, and infection, even if Covid experienced a significant number of mutations. Plus, the lower pathogenicity of Omicron would give it a survival advantage across populations, given that it would be less likely to kill its hosts. All that being said, while this prediction turned out to be somewhat true and the pandemic has remained stable after that point, with deaths and hospitalizations staying relatively stable in the US (albeit at a high level), and all subvariants being offshoots of Omicron, the 2021 winter Omicron wave caused a high rate of hospitalizations, deaths, and cases, even if it induced immunity in the process. 

So you might be wondering, what exactly was the point of going down memory lane with Covid? What was the point of discussing all these events? What I hope that you gleamed from this article is that while the Covid-19 Pandemic had an end of sorts, and while we appear to be out of the unstable, uncertain phase of the Pandemic now, America’s response fell quite short in many ways. Any future Pandemics could be made worse, and if we do not focus on how to significantly improve our response, the level of suffering that we undergo then could be made way worse. For one, we needed to be way more proactive, not reactive. We needed to stop hoping that Covid would end by itself, and we needed to actually take the steps to end it. We needed to tightly restrict travel from other countries and put a lot of security measures in place to prevent variants from coming to our country. Similarly, we needed to distribute the vaccine much more equitably and put a much more all hands-on deck effort in getting the world vaccinated by early 2022. It would not have been easy, but it could have been done. Additionally, we needed to keep slight restrictions in place until the world was vaccinated, like having a Federal Mask Mandate to keep cases as low as possible, while vaccinating the world. Finally, with the level of genomic analysis that we have available in today’s day and age, we should have worked on predicting worst case mutations that Covid-19 could undergo and created backup vaccine formulas based on those mutations to have immediately ready the second that we heard of these new variants. All of that would have minimized the level of hospitalizations, deaths, and disruption that society had to undergo throughout this pandemic. So, if nothing else, I hope you as a reader takeaway one point from this article: We needed to do way better in our response, and we are lucky that this was not way worse than it already was!

Sources:

Lubell, Maayan. “Israeli Studies Find Pfizer COVID-19 Vaccine Reduces Transmission.” Reuters, Thomson Reuters, 19 Feb. 2021, www.reuters.com/article/health-coronavirus-israel-vaccine-int/israeli-studies-find-pfizer-covid-19-vaccine-reduces-transmission-idUSKBN2AJ08J/.

De-Leon, Hilla, and Dvir Aran. “What pushed Israel out of herd immunity? modeling covid-19 spread of Delta and waning immunity.” medRxiv, 2021, https://doi.org/10.1101/2021.09.12.21263451.

 

 

 

 

At the Atlanta Science Festival, me and my team members, Ashmita and Claudia, had the pleasure of getting to talk about Heat Stroke to a large audience of individuals and explain the seriousness of it, and why it’s so important to pay so much attention to it and take so much initiative to prevent it. Not only did I enjoy this experience because it gave me experience speaking in public in front of a large group of family members! But, in doing so, I myself actually became more interested in the topic and its political, social, and economic implications. Being a Biomedical Engineer, this topic also hit close to me as it reminded me of a pressing global problem, where the solutions still have significant limitations in their capabilities and how accessible they are all around the world, an issue that I commonly learn how to tackle throughout my degree. In this post, I hope to do two things. I hope to share the information and insight I learned about heat stroke with those who were unable to come to the Atlanta Science Festival. Second of all, I hope I can share with you some of the ways I have thought about solving this pressing problem of Heat Stroke and my thought process to go about solving it!

First of all, many of you are probably wondering, haven’t we all dealt with Heat Stroke? After all, Atlanta is perpetually hot all the time! Heck, it’s just the beginning of May and it already feels like it’s 140 degrees. However, as miserable as that might have been, I promise you that that was not Heat Stroke! What you likely dealt with was Heat Exhaustion, which is extremely uncomfortable, but I promise you that it is not nearly as bad as Heat Stroke! With Heat Exhaustion, at least your homeostatic mechanisms are still working. You know your Homeostatic Mechanisms, the ones that ensure that your body is still in balance, even with changes in the environment to prevent you from developing diseases or dying?! Do you remember how, for instance, when you have gone and exercised quite a bit or you have been outside in the hot sun for some time, you have sweat quite a bit? These are examples of your homeostatic mechanisms kicking in, so you do not have a detrimental response to these environmental changes. The problem, though, is that like everything in life, these mechanisms designed to protect you can fail. Eventually, the hypothalamus, which is responsible for maintaining this homeostasis gets worn out. When that happens, you are basically exposed to this significantly increasing temperature, without any defense mechanism to fight back (Garcia 6). At that point, you are essentially overheating like a computer which is something that can lead to significant consequences, including death, which I will discuss as we go forward!

So now that you know the difference, the next thing that you are probably doing is, what can we do to better deal with the increasing incidence of Heat Stroke in our society? First of all, healthcare providers in our society have to do a better job of treating Heat Stroke with the same level of urgency as other critical illnesses and have to treat it more like diseases, such as Appendicitis, where you will immediately die if you do not get the necessary surgery. This is extremely similar to that. In the case of Heat stroke, not getting treatment immediately can lead to muscle, kidney, heart and even brain damage. The other side of this argument is that more effort has to be taken by the individual to prevent the detrimental consequences of heat stroke and take early action before it is too late, and there are significant, everlasting effects. Simple steps may seem inconvenient, but they can ensure prevention of the worst outcomes from heat stroke. For instance, steps, such as drinking enough fluids, looking out for health related problems with medications, applying sunscreen, and avoidinging overworking in the heat can go a long way. Additionally, significantly more funding has to be spent by the government in investing in the protective equipment necessary to effectively prevent heat stroke as investing money in vaccines, and treatments for other diseases. While two solutions, besides just protective equipment, Neck Fan and the Ice Pack, have gone a long way in attempting to prevent and mitigate Heat stroke by helping to constantly blow cold air around a person’s neck, so as to help that person cool off and bring their body temperature down and reducing body temperature by promoting the contraction of blood vessels; thereby, ensuring that joints are less stiff and that muscle spasms are less likely to occur, these solutions have limitations in the long-term. Eventually, an issue will arise with long-term use of these interventions and something more will need to be done to prevent a significant rise in temperature in just a short period of time. This is especially true for individuals who are in jobs that exposes them to significant amounts of heat on a chronic basis (Kim 4). Additionally, while current PPE are effective in preventing certain infections, they also add to the problem of heat exhaustion and heat stroke (Steps to Put on Personal Protective Equipment (PPE).” World Health Organization, World Health Organization).

This is where research from Georgia Tech and other universities in this area has come to extremely significant use in helping to create longer-lasting and more effective solutions. The solution from Georgia Tech researchers resulted from a way of thinking that was completely outside the box of the problem, but got to the heart of what was necessary! Tech researchers have found that with the creation of a sensor system, through the utilization of a cloud based sensor system, not only can heat stroke be treated effectively, but its incidence can be significantly reduced to begin with (GTRI Helps Develop Wearable Sensor System to Prevent Heat Injuries among Soldiers). Trust me, this technology is way too much for me to understand! However, the gist is that researchers will be able to obtain information about changes in soldiers’ temperatures over significantly large distances. Too large of a heat increase in too short a time will still be a problem. Make no mistake! However, the hope is that if a rapid heat increase is detected before it becomes an extreme issue, a soldier can get the help that they need to prevent complications (Foy 2). This is especially true with the use of local networks, which should be able to tell a soldier whether there are any soldiers in close proximity to them that can assist them. In the long-term, I hope that I can build upon this work to create an internal cooling mechanism to bring down the temperature and a method to help predict baseline normal temperature, based on the thickness of the suit and the environment an individual is working in. For now, though, I hope I have at least been able to better provide insight into why Heat Stroke is such a big problem and why it is one that both more individual and societal effort is needed to solve!

Citations:

1. Akins, Anna. “GTRI Helps Develop Wearable Sensor System to Prevent Heat Injuries among Soldiers.” Institute Relations, https://gov.gatech.edu/node/515.
2. Cecile Garcia, Operations Manager. “Feeling (Not so) Hot: Heat-Related Conditions and Illnesses.” Blog, Joffe Emergency Services, 14 June 2019, https://blog.joffeemergencyservices.com/event-medical-services/feeling-not-so-hot-heat-related-conditions-and-illnesses. 
3. “Steps to Put on Personal Protective Equipment (PPE).” World Health Organization, World Health Organization, https://www.who.int/bangladesh/emergencies/coronavirus-disease-%28covid-19%29-update/steps-to-put-on-personal-protective-equipment-%28ppe%29. 
4. Kim, Siyeon, et al. “Frequency of Firefighters’ Heat-Related Illness and Its Association with Removing Personal Protective Equipment and Working Hours.” Industrial Health, U.S. National Library of Medicine, 4 June 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546580/. 
5. Foy, Kylie. “New Device Detects Heat Strain in Military Trainees.” MIT Lincoln Laboratory, https://www.ll.mit.edu/news/new-device-detects-heat-strain-military-trainees.

 

Imagine that you’re a Georgia Tech student. Your day starts at 8:25 AM, with your first class, Systems Physiology, which you know you have a weekly quiz in. You wake up at 8:05 AM, and by the time you finish brushing your teeth and changing into your clothes, you see that is 8:10 AM. Your class is not nearby. These are not the times of virtual classes after all! You have to make it all the way across campus, and you have barely any time to do so. You can’t take the bus because the bus is running late. So, you are unfortunately left with only one choice, to run quickly to class and skip breakfast, or eat breakfast, miss your quiz, and hurt your grade. Which do you pick? The answer that many students at Georgia Tech would pick would be to skip breakfast. After all, your stomach can wait right? Your hunger can wait? So what that you don’t eat for a few hours, what is really the worst that can happen? Eventually, skipping breakfast leads to skipping lunch because you are too busy throughout the day to eat lunch, and eventually, next thing you know, you’re skipping dinner because there’s no time to eat any dinner. You have that test to study for that’s happening in the morning that you need to ace, and you can’t even waste a second taking a break to eat. This is unfortunately the reality for many Tech students, and college students, in general, and I hope to tell you today why this reality is so dangerous and the significant harm that it can cause.

Sure, one or two days of late eating or skipping meals may not harm you. Heck, even if you do it for a few months, nothing might happen. However, what I am here to tell you and what I hope to instill in your minds today is that this is not something that you will get away with over the longer term. Contrary to what you may have been told, your digestive system is not ironclad. Just like other parts of your body, your digestive system is prone to diseases and issues. You just don’t realize it because, well, how could you? When your digestion is working as it should, you are less inclined to pay attention to it because you are not in a constant state of pain or distress. It is only when things go wrong that you start to realize how truly important eating properly is, and the impacts of not eating properly. Over time, not eating properly can wreak havoc, not just on your digestive tract, but ultimately your entire body. In fact, not eating properly can be a risk factor for many chronic diseases in the digestive tract and throughout the body that can ultimately increase the risk for cancers, autoimmune conditions, tissue damage, etc. if they continue long enough.

Perhaps, one of the most devastating consequences of chronically undereating, caused by skipping meals is the development of a condition called Gastroparesis. Gastroparesis is a condition that is caused, when the stomach empties significantly more slowly than it should. Think of it this way, normally when you eat something like a sandwich, over 90% or so of that sandwich should be gone from your stomach within 4 hours. Put another way, if someone were to take a look in your stomach after four hours, they should see almost none of the sandwich there. Contrast that to someone with Gastroparesis, where, even after 3 to 4 hours, a noticeable amount of that sandwich may still be remaining in that person’s stomach (perhaps, even as much as 40% to 50% of the meal, or, in some cases, even more). Now, you might think, surely it’s not that big of a deal that your stomach takes longer to empty? What’s the worst that’s going to happen? You’re going to feel a little more full for a little more time, so what? Unfortunately, the symptoms are usually much more severe than this and most people feel much more uncomfortable than just feeling full for a longer period of time. When the stomach does not empty as it should, many people can feel nauseous, have stomach pain, feel like their stomach is overly stretched for long periods of time, etc. (Gastroparesis).

Additionally, the discomfort of Gastroparesis does not just stop with the symptoms of the disease itself. Many people who have Gastroparesis are at risk of developing a significant complication known as a Bezoar. This is when undigested food matter essentially forms a large clump in your stomach or your intestines and effectively blocks the flow/passage of other food or fluid (Palchaudhuri 26). One example is a Phytobezoar, which is made up of matter from cellulose and other cruciferous vegetables that are poorly digested in those with impaired gut motility. There are other types of Bezoars, but the key theme with all of them is that they can be life threatening if not addressed immediately because they can prevent the delivery of nutrients to your tissues. Gastroparesis can also affect your blood sugar levels. You may not think about it, but, usually, when you eat, your stomach moves food to your small intestine throughout the day, keeping rises and falls in your blood glucose levels extremely stable. However, for someone with Gastroparesis, when food that is stuck in the stomach for so many hours suddenly moves to the small intestine all at once, all that sudden absorption of large quantities of food can cause such a significant and rapid increase in Blood Glucose levels. This can have extreme complications, such as causing Ketoacidosis, and causing rapid cell shrinkage, due to a person’s blood becoming significantly more concentrated than it was before(Shakil and Church 1699).

So now that you have heard so much about Gastroparesis, you are probably wondering, how does skipping meals cause Gastroparesis? How does my stomach suddenly lose its ability to digest food properly, just because I skip meals? Well, it turns out that the answer is actually much more logical than you might think. Just like other muscles in your body, the muscles and nerves in your stomach need to be used periodically in order to effectively work. Just like other muscles and nerves in other parts of the body, the muscles and nerves in the stomach atrophy or weaken when they are not being effectively used. For example, have you ever seen the movies about children who were in wheelchairs all their life, and then suddenly tried to walk? Did you notice how it took these children a very very long time to learn how to walk afterwards? Similarly, have you noticed how when you lift weights at the gym, you build muscle, but after a period of time, when you stop working out, you end up losing all that muscle? This is a natural consequence of muscle atrophy. Believe it or not, the same thing happens in your stomach. Moving food is essentially the work out for the muscles in your stomach, and if they stop getting this work out, they get weaker and weaker (Santonicola and Gaglidari 10). To an extent, these muscles can become stronger again by being used again, through eating properly, but it is a slow and difficult process and it is one that I don’t think anyone should have to go through, especially for something this preventable.

So why did I tell you all this information about a random health condition? Well, my intention was not to scare you, but rather just to convey that taking care of your physical health is just as important as success and grades. These days, so much stress is put on our age group to meet certain expectations that I think we forget the importance of taking care of ourselves sometimes, and that is really a significant problem in and of itself. The incidence of many diseases in young people are rising, especially in the western world, and one significant factor is that, these days, young adults are so stressed out that they do not take the time to put as much effort into their health or their physical and mental well being, as they do their success. So, I hope with this post, I have emphasized that not taking care of your health can have significant consequences and is just as important as being successful in school and other facets of life.

Citations:

Chawla, Rajeev. “Gastrointestinal Complications of Diabetes.” Complications of Diabetes, 2012, pp. 100–100., https://doi.org/10.5005/jp/books/11685_10.