RESEARCH AT EXETER:
INTERVIEWS WITH AYUSH NOORI AND EMILY GAW
By: Lina huang
Ayush Noori
Could you tell me about your research?
I studied Alzheimer's, Parkinson's and ALS, or amyotrophic lateral sclerosis, also known as Lou Gehrig's disease. Currently I'm working on two major initiatives. The first one centers on cells called astrocytes and microglia, or the neural support cells in the brain. These cells are known to have a distinct phenotypic reaction to Alzheimer's, which may underlie disease pathogenesis. Therefore, we are using human brain tissue to elucidate the specific driver drivers of this phenotypic change, which is commonly known as astrocyte reaction or astrogliosis. The other project I'm working on is an analysis of human transtomics data across Alzheimer's, Parkinson's and ALS to identify both shared mechanisms of pathology as well as disease specific expression signatures.
I'm working at Massachusetts General Hospital and Harvard Medical School, and specifically in the Institute for Neurodegeneration and the Massachusetts Alzheimer's Disease Research Center. We're using human brains, and what is called formalin fixed paraffin embedded sections of those brains to perform a special process of immunohistochemistry. We found some very interesting results which point to novel candidates, which warrant further investigation as drivers of astrocyte reaction and microglial reaction.
For the other project, I’m doing a meta analysis across publicly available data sets and applying bioinformatics techniques to identify a pan-neurodegenerative expression signature. It is well known that across neurodegeneration, there is shared morphology. If we can identify what the specific mechanisms that are common to Alzheimer's, Parkinson's and ALS, we can reveal the processes at the cellular level which are driving neurodegeneration most centrally, and also look at which processes are specific to one disease over another.
Here at the Academy, I constructed an open source, semi automated, high throughput robotics platform called the Wormbot for lifespan and mobility analysis of a nematode called C. elegans. We're analysing the genes using graph topology analysis of pathway data and differential expression data. In the metaanalysis, I’m doing differential expression, pathway analysis, subsequent downstream analysis, and then meta analysis. I'm using some of the output of that analysis, performing graph topology, analysis, and identifying what are called intramodular hub genes. These are the genes that we think are most central to the disease process, and then we're using RNA interference or RNAi, as well as other techniques, to knock these genes down in C. elegans models in neurodegeneration. Then the robot measures their health, if you will, so it would get quantitative scores for the impact which a specific gene has on the disease process. I've been working on this project for a long time now, but I'm continuing my work as a senior project this term. I did a 999 last spring in biology.
What got you interested in this research?
I started researching neurodegeneration because my grandmother suffers from progressive supranuclear palsy, which I often say is Parkinson's on steroids. The average life expectancy for a PSP patient is five to seven years, and she was diagnosed more than a decade ago. She’s in the end stages of the disease. And growing up, I helped with her care, I helped nurture her and we're very close, so I'm very intimately familiar with the devastating impact that neurodegenerative disorders have on both patients, families and caregivers. So, always centering your focus back to the patient helps to fuel passion for the work.
This is what started it, but I immediately fell in love with biology. I see infinite beauty in biological order, and it amazes me endlessly. One of the most formative courses was the bio 510 520 530 advanced biology sequence because it gives you the fundamentals to explore any topic of biology in greater depth as you please, so I think it's among one of the best courses I've taken at the academy and redefined me in certain ways as well.
What has been your favorite part of the research?
When the results show you both expected and unexpected things. When it shows expected things, it's good validation of the work that you've done. When it shows unexpected thing, it’s concerning at first. When it shows both expected and unexpected things it's exciting because you hope that it's one step further in the fight against neurodegeneration.
What got you interested in microglia specifically?
The microglia are emerging candidates for exploration in the field as a whole. It's these sort of focal topics which are most likely to generate therapies for patients. The other thing is we're in the midst of a big data revolution; the amount of data that is being made available for patients is absolutely remarkable, so increasingly, the problem is not collecting the data, although of course, that's still a challenge. The problem is how do we extract meaningful, relevant biological signals from the data and so learning those tools has been an invaluable resource.
What advice do you have for high schoolers who want to do research?
Come to Bio Club. We are working on some bio research projects and will help you get your feet wet. The second piece of advice is don't be afraid to cold email people. I've had a lot of mentors who took a chance on me and who have dedicated a lot of time and support and resources to my work, and I'm very grateful for that. The third thing is it's not easy: don't lose faith because you don't see results immediately. Research is a long haul, and the end is very rewarding. When you see a patient impacted or even given hope because of a discovery that you've made, that's worth it, so don't don't give up.
Emily Gaw
Could you tell me about your research?
I'm performing research on the insulin signaling pathway in the roundworm C. elegans. The pathway has been proven to have effects on longevity and also diseases such as diabetes and cancer. Previous research has been done on administering glucose to these worms throughout their lifetime which decreases their overall lifespan. My research differs because I am administering glucose periodically over time and through different methods of exposure. I hope my research might be able to contribute in some small way to creating more personalized treatment for disease in the future. I’m collecting data on lifespan, fecundity or egg laying, and lipid accumulation.
What got you interested in this research?
I became interested initially because my grandparents on both sides have had dementia. They both have difficulty eating. My readings indicated that insufficient nutrition can trigger dementia. I also think it's important to research the effects of glucose, something that plays a role in everyone’s daily life. The study of longevity also strikes me as a fascinating topic within Biology in general, and I was drawn into it immediately when I started research. During the summer after Lower Year I attended a camp that gave me the opportunity to work with C. elegans and an avenue through which to explore these connections.
What were your results?
It’s really interesting, because in previous studies scientists have found that constant exposure to glucose shortens the lifespan of worms, but I found that with different exposure methods and patterns, longevity doesn't necessarily have a negative correlation. At first, I felt like there may have been an error, but I've repeated the experiment four times now and have gotten the same results. More often than not, the worms given high levels of glucose in a certain pattern live as long as the control worms. The other fascinating observation was that worms given glucose, then removed from glucose, live shorter amounts of time than worms re-exposed after being taken off. Once they're exposed to glucose, it seems to be impossible for them to re-adapt to a non-glucose normal environment. I've also been doing some inter-generational studies, but I don’t have enough data at the moment to offer conclusive results. I want to research that further.
What has been your favorite part of the research?
Writing a summary paper at the end and analyzing my data. Performing the experiment and being in the lab is fun, but I think the importance of research really strikes me when I look at my data and observe trends - especially when the data has outliers or unexpected new correlations. Another favorite part is the effort to try to understand where the trends are coming from, scientifically, and formulating future experiments to address outstanding questions.
What have been some challenges for you?
The amount of time that it takes to perform an experiment, especially in high school, has been challenging. I have to move my worms to new petri dishes every day and carving out this time at Exeter has been challenging, but it's so worth it.
What got you interested in science?
I’ve always been fascinated by the ways and reasons things work. I also really enjoy watching TED Talks, which have further sparked my curiosity about science. I like looking for paradoxes and attempting to solve problems, so research really stood out to me. I also love hearing about amazing scientists pioneering research in new fields.
How has Exeter facilitated your research?
Exeter has been so accommodating and has allowed me to use their lab last year to perform my experiment. My project advisor, Ms. Rankin, has also been an invaluable resource. She was always available for me to talk to and helped me with all my troubleshooting. Exeter also provided a community where I could share my research through STEM Day last year.
What advice do you have for high schoolers who want to do research?
I feel like a lot of people think that performing research is unachievable, but you really just need Google, curiosity and a few emails to get started. As long as the research you want to do is not something that's actually dangerous to your health, teachers go out of their way to support students and their interests. The main thing about having a research project is to find a subject you feel passionate enough about. From there, you will be able to accomplish anything. Even if you don't feel research is within your reach, but it really is!