Graduate / Application essay for PhD in Biological and biomedical sciences [3]

This is a great forum and I would like to contribute whatever I can to other essays. Following is an essay for admission to Biological and Biomedical Sciences doctoral program. I think the introduction is not very captivating. I am thinking of bringing in the part about how I went back to research after employment in the introduction, by rephrasing it. It will explain my passion for research right in the beginning. For example, my boss at work once said "No need to put in so much thought into it" when I came up with a new ideas, quite contrary to what I thought a job would involve. I didn't want to have a career where there is not much scope for innovation. Something on these lines.

Please let me know any comments and criticisms right away!

On a recent visit to my school, I saw my project of an animal cell model propped up in the biology lab. My teacher explained that he had chosen it as the best project because it was the only 3D model clearly showing not only the cell's contents, but also the structure of the nucleus and cytoplasm through sections. All the other students had only made flat replicas of the text-book figure. This experience brought back vivid memories of how the structural facets of life fascinated me even as a child, and continue to motivate my educational and professional journeys.

In college, I took a biophysics course due to my interests in macromolecule structures. Imagining the macromolecules in space, I would try to associate how charges, physical forces and topology guide structure, dynamics and binding. On a macro scale, it was interesting to learn about how flux balance brings about coordinated regulation in a metabolic network in the enzymology course. I was enticed by the holistic view of a system given by its network topology, such as its sensitivity and robustness to fluctuations.

I find many aspects of biology interesting, and, the inter-relatedness of the sub-fields makes it hard to delineate areas of interest. However, for graduate study, I would most like to pursue research in the following three areas.

Within structural biology, I am particularly amazed by the seemingly simple, uniform and stable structure of the DNA molecule and storage, replication and retrieval of genetic information. Is there extra information coded into this molecule that guides not only gene expression, but also its regulation? What higher order structural or chemical information is present in DNA and chromatin? How do DNA-binding proteins extract this information? What structural mechanisms are involved in binding of proteins and regulation? Why do proteins bind and regulate at certain sites and not others? What are the characteristics of regulatory sites?

I am also interested in studying factors involved in the precise and efficient regulation of biological systems through quantitative tools of systems biology. What mechanisms cause high expression of a gene in one tissue but low expression in others? Is it only the consensus sequences that guides DNA-protein binding or do other factors like stoichiometry of interacting molecules or mechanical forces come into play, too? How does the co-ordinated regulation of these factors bring about desired expression?

A final area of interest involves studying structure and forces acting at the cellular or tissue level. How is the cargo transport inside cells regulated? Which chemical and physical forces acting in cell-cell or cell-matrix interactions lead to differentiation, cell adhesion and motility? What mechanisms are involved in cellular response to mechanical stimuli? Are mechanical signals involved in signalling and regulation in certain cells, such as embryonic cells?

I have tried to explore few of these questions in my current research project. I am working on a project with XYZ at the XYZ Institute in collaboration with the ABC Company, where I am able to pursue my interests in DNA structure and gene regulation. Working on this project and surveying the literature, I have come across evidence indicating that DNA structure may play a major role in determining cis-regulatory sites. The project aims at predicting promoters on the basis of DNA structural aspects, which are determined from di and tri-nucleotide sequence. Yet regions showing characteristic structural patterns do not show any consensus sequence. In this project, I learned programming for parsing and number-crunching in order to analyze genome-scale data. Also, while fine tuning the program, I learned how to consider and interpret negative results to figure out what is going wrong. Our analysis has yielded interesting results that are being incorporated into a manuscript. I am enjoying working at the forefront of discovery, trying to find solutions to unsolved problems.

In my Master of Science thesis project, I carried out docking simulations using statistical mechanics. I learned about how global and local searches can be employed to arrive at minimum energy conformations. I also learned how stochastic search methods help reduce computationally intensive calculations for arriving at energy minima. It also helped me develop troubleshooting and analytical skills, which are vital for research. The program I used could dock only one molecule at a time. In order to dock both donor and acceptor to a glycosyltransferase, I used the transition structure of the transferase reaction as the ligand.

My thesis project was a great learning experience and my first venture into computational biology. However, I had audited extra courses that semester to enhance my knowledge, considering the effect it might have on my GPA as a compromise. Also, there was a lag phase of learning in the project and I was not able to achieve satisfactory results in the short duration of the project. Hence, I decided to work on the same project in the summers after graduation. Building upon the knowledge and skills gained earlier, I was able to deduce the acceptor binding site and binding conformation within a month's time.

Through my experience, I have seen how computational power can help in simulating reality to best possible approximations in order to get results much faster than by actual experimentation. This can help in arriving at guiding principles for experimental work. At the same time, experimental analysis is required to verify results or take the project to the next level. The acceptor binding site predicted in my M.Sc. project is now being tested in the lab. Also, the ABC Company will carry out experimental analysis of promoters predicted with high precision. In the future, I would like to apply both experimental and computational approaches in research or form collaborations with other scientists.

Any kind of work requires sincere interest and passion. After my master's, I took a job to give me time to think over my plans and explore alternative career options. Working as a patent professional in a multinational company gave me exposure to patent procedures and a taste of corporate life and global culture. But I soon realized that I yearned to be at the forefront of discovery that I was reading about in the patents. Returning to a research setting, I was much happier and enjoyed the work, despite much lower compensation. The stark difference in my happiness levels made me realize that research is my true calling.

A strong educational background in biology, along with training at the interface of biology, chemistry and computation, has prepared me for graduate study in interdisciplinary fields. I am sure my interdisciplinary background will help me think beyond conventional boundaries while addressing problems in research. In the future, I would like to be involved in exciting research in academic or industrial settings. Also, I would like to pass on my knowledge and findings to future generations through teaching.

I would like to join the XXX program within XXX University primarily due to its interdisciplinary nature of studies and breadth of research areas available. There are many faculty, such as X,Y,Z with whom I would like to work. Graduate study at XXX will give me an opportunity to pursue my interests in systems biology and structural biology through interdisciplinary approaches. It will also allow interactions with students and researchers with diverse educational backgrounds and interests. I look forward to honing my skills and knowledge through working in the exciting research environment in the XXX program.