Sample cover letter for Full Time position at University of Cincinnati

It still intrigues me why medical science is yet to come up with the right answers to

diseases like cancer. As an undergraduate student in Pharmaceutical Sciences, I learned that anticancer

drugs address a bizarre number of diverse targets, whose identification are of paramount

importance. Conventional laboratory experiments have limitations in validating these targets, and

are heavily dependent upon computational methods, to come up with solutions at the molecular

level. With this in mind, I resolved to pursue my Master’s in Pharmacoinformatics (Bioinformatics)

at National Institute of Pharmaceutical Education and Research (NIPER), a premier learning and

research institute in India.

During my Master’s, the field of Systems Biology aroused my passion. Through this field,

I could identify my long-term interest in doing advanced research on biological disorders. As I

explored the area, I found it fascinating when I recognized that the modeling approach provides a

shift from treating a disease target to treating pathways.

As I delved deeper, I found another field

that uses similar computational approach: Computational Neuroscience. I delivered a seminar on

the topic in my second semester, which was critically acclaimed by my mentors. Through my

studies in computational neuroscience, I learned the importance of multiscale modeling in exploring

nonlinear systems. The differences between the two fields are apparent, but I do appreciate that

understanding a system as whole as well as individual components is necessary to deal with

biological disorders.

My Master’s thesis involved a nine-month research project under the supervision of Dr.

Gautam Basu, Professor at the Department of Biophysics at Bose Institute in India. We were

addressing substantive questions about tubulin, a globular protein of interest as a target for anticancer

drug therapy. From an analysis of tubulin sequences and ligand-tubulin crystal structures, we

found that family-specific ‘signature’ residues on ligand-binding sites of tubulin are crucial for the

differential ligand-tubulin interactions across eukaryotic families (animals, fungi, protists, and

plants), and can thus provide insight into the evolutionary origin of small ligands binding to tubulin

in animals. We employed mathematical procedures to exploit the pattern for prediction of

functional residues in tubulin sequences, using formalism of Principal Component Analysis (PCA).

To understand the effects of mutating residues in yeast tubulin, we built homology models of wild

type tubulin dimers of yeast and its mutants (with MODELLER). Attempts were also made to gain

insights into subtle differential structural changes between animal and yeast tubulin (and its

mutants) using molecular dynamics (MD) simulations (with GROMACS). I specifically used

FORTRAN (G77 on Mac OS X) codes to process sequence data, which afforded large data

compilations in quick time. My background knowledge of molecular biology, computer science,

chemistry and biophysics came good for undertaking this research.

Now I want to do further in-depth studies on numerous biological phenomena, including

protein folding, macromolecular interactions and flexibility of ligand binding. I am also interested

in understanding the specific functions of biomolecules and complexes associated with biological

systems and disorders. I believe I can make good use of Molecular Modeling, MD simulations,

docking and such other techniques I am familiar with. At the same time, I am also eager to learn

other effective computational techniques like modeling signal transduction, metabolic and

interaction pathways to simulate several disease conditions, and utilization of assorted expression

data to model biological networks.

I am convinced that for profound understanding of biological problems, it would be

necessary to work with multiple disciplines in a concerted manner. I believe Systems Biology

provides that interface, acting as a link between Bioinformatics and Computational Biology. Given

my research experience and knowledge base, I am keen to participate in innovative biomedical

research and eager to take up the challenges and rigors that entail such activity.

University of Cincinnati is one of the leading academic health centers in United States of

America. From the website at the College of Medicine, I find that the Ph.D. program in Systems

Biology and Physiology under Department of Molecular and Cellular Physiology (MCP) provides a

lot of latitude and flexibility. What excites me is the wide range of research being conducted with

collaborations, interdisciplinary approaches and sharing of resources. In the backdrop of my

education and research interests, I can relate to some of the ongoing research at University of

Cincinnati. I am keenly interested to participate in the present research conducted by groups of Dr.

Jaroslaw Meller on Molecular Dynamics studies of replication protein A; Dr. Mario Medvedovic on

development of mathematical models based on Bayesian infinite mixture models from functional

genomic data; and Dr. Bruce J. Aronow on

modeling biological systems to decipher how they

assemble, adapt and become impaired in diseases. Since there is very limited ongoing research on

these wider aspects in my country, I feel that I would get a better scope for further research at

University of Cincinnati.

I wish to advance my research career at University of Cincinnati. I am convinced that

through participation in the Ph.D. program in Systems Biology and Physiology, I would be able to

harness the immense opportunities available there, which will further my goal towards coming up

with relevant solutions to diseases like cancer. Furthermore, I believe that I can contribute to the

community at University of Cincinnati in a significant way through my research and my

collaborative efforts.