I Program in Physical and Engineering Biology

I am applying to Yale’s Integrated Graduate Program in Physical and Engineering Biology
through the Department of Mechanical Engineering & Materials Science to pursue my interest in
approaching biological research from a physics and mathematical perspective.
Since high school I have known that I wanted to be a scientist and I have planned my
undergraduate curriculum accordingly. I started as a physics major and soon added a second
major in quantitative biology. In addition to physics courses, I have taken courses in molecular
biology, genetics and biochemistry as well as computational mathematics and probability and
To gain research experience as soon as possible, I joined the computational biophysics
group of Dr. Edward Lyman in the Department of Physics and Astronomy the summer after my
freshman year (2015). Dr. Lyman’s group studies the dynamics of lipid membranes by using
molecular dynamics simulations. My project involved modeling a phospholipid bilayer to pinpoint
its gel-fluid transition temperature. The project has resulted in the publication of a paper in the
Journal of Physical Chemistry B, November 2016, of which I was a coauthor. In that work I
developed and tested a method to control the initial state of the system by optimizing the initial
temperature. This technique was then used extensively in the rest of the project. Through this first
research experience I learned general aspects of membrane biophysics and computing, which
confirmed my plans to pursue a career in research.
Returning the next summer, I started a new, more involved project. Its goal was to
characterize the interaction between cholesterol and G-protein-coupled receptors, again using
molecular dynamics. In this study I analyzed simulations where cholesterol molecules sample
different binding configurations on the surface of the receptor and I developed an algorithm that
scored residues of the GPCR according to the level of cholesterol interaction both spatially and
temporally. This analysis effectively predicts where cholesterol interacts with the protein, which is
important to know because cholesterol regulates GPCR activity. From this project two new
interaction sites were identified and reported in a publication in the Biophysical Journal, where I
was the first author. Seeing “Rouviere et al.” for the first time made me very proud and has further
encouraged me to pursue a PhD. I am extending this research for my senior thesis. I am currently  applying the analysis to 14 other GPCRs to see if the identified interaction sites are conserved
across the GPCR family and confirm that they are key to the regulation mechanism.
Through my involvement with the Lyman group, I have given several poster
presentations, one at the Annual Biophysical Society meeting, and I gave a talk at an American
Physical Society regional meeting.
My research experience in the Lyman group has shown me how exciting a physics
approach to answering biological questions can be. With experience in physics and
computational research, next I wanted to try some experimental biology. I joined a microbiology
lab under the supervision of Dr. Julia Maresca in the fall of 2016. In my project I worked on
developing a fast yet robust way to quantify via fluorescence the amount of actinorhodopsin
expressed in natural bacterial populations. We used TIRF microscopy to image the membrane
surface of bacterial cells and to quantify the amount of fluorescence that a single actinorhodopsin
complex emits. In addition to imaging techniques, this work involved tuning the expression level
of actinorhodopsin in cells using techniques of microbial physiology and molecular biology.
Last summer (2017) I worked in the lab of Dr. Sven van Teeffelen at the Pasteur Institute
in Paris. His lab studies how bacteria regulate their shape and size during growth. Bacteria are
encapsulated by a rigid cell wall and it is the cell wall that defines their shape. My project focused
on understanding the effect of the peptidoglycan hydrolase MepS on the morphology of the cell.
To this end, mepS was put under an inducible promoter so that the levels of MepS production
could be modulated with an inducer. Using phase contrast microscopy I imaged the cells that I
had grown under various mepS induction levels. I wrote an analysis program to measure the cell
diameter, length and curvature from the images. Although we experienced unexpected
challenges in the project and were not able to complete it by the end of the summer, I believe I
contributed to troubleshooting and optimizing the experimental parameters by testing my ideas
and ruling out potential problems. This experience at bench research has made me realize, even
more than I had in computational research, the importance of attention to detail, clear thorough
planning and the need for systematic methodology.
I have enjoyed seeing how a theoretical approach to answering a biological question can expose the underlying structure of a system and thus allow for a deeper understanding and help
guide complementary experimental approaches. From applying statistical mechanics to describe
virus capsid self assembly to using nonlinear dynamics to model cell interactions in microbial
populations, I find the quantitative approach to biology fascinating. After college, I want to
continue my education in graduate school to develop tools that I will use to explain complex
biological phenomena. The PEB program in conjunction with the Mechanical Engineering
Graduate Program offers the exact training I am searching for: a highly interdisciplinary program
that can be tailored to the needs of the student at an institution. I believe that my success in my
undergraduate courses and my accomplishments in my research prepare me well for a rigorous
training in graduate school and also predict my continued success in the future. Presently I am
very interested in the work of Corey O’Hern, Thierry Emonet and Murat Acar who, although all
work on different problems in biology, all employ quantitative methods of theory and computation.
After completing graduate school I hope to pursue a career in academia and I believe that the
Graduate Program of Mechanical Engineering and Materials Science with a concentration in
Physical and Engineering Biology will be fundamental in helping me reach this goal.


I'm Isaac!

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