Understanding The Complexities Of Life Education Essay

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My schooling and college was very important factor in shaping my career. Excellent grades in board examinations, 83% in 10th grade and 82% in 12th grade, always kept me in top 5% of the school. Excellent faculty, which always focused on the fundamentals, motivated me to study harder and with complete understanding of the subject. In my college, I became particularly interested in the field of Biology as I was always amazed by the diversity and complexity of life around me; I chose to study biology in more detail. I chose Biotechnology as my major for my bachelor's degree (B.Sc.) along with chemistry and zoology as minors. Biotechnology helped me understand applied biology in great details. I also attended an on job training under Annual Biotechnology Training program at Haffkin Institute, Mumbai where I got more exposure to practical biotechnology, different biophysical techniques and instrumentation. Parallel to all this, I was also interested in computers right from my school days. A course on programming in C, gave me an opportunity to learn computer programming and its applications. Having heard of bioinformatics as a combination of biology and computers, I applied for and got selected through large number of applications to attend a workshop on bioinformatics at Indian Institute of Technology (IIT), Mumbai. Here, I was introduced to power of computers to answer questions in biology. My understanding of biology, love towards computers and insight into the world of bioinformatics and its applications through my curriculum and the workshop worked as a strong motivation for me to choose the specialization for my master's degree. I determined to pursue my further studies in the field of bioinformatics and computational biology with an aim of utilizing potentials of computer systems and of recent advancements in the field of information technology in order to study biology with more ease and at accelerated rate.

I was selected to pursue my Master of Science (MSc) in bioinformatics at Bioinformatics Centre, University of Pune, India, through a nationwide entrance examination. I was ranked 8th from around 1000 applicants who appeared for the test. My consistently good performance in entrance test and in subsequent semesters made me eligible for Prof G. N. Ramchandran fellowship and Dept. of Biotechnology, Govt. of India scholarship to pursue my master's degree education. Bioinformatics centre is one of the premier institutes in India which is renowned for its contribution in the bioinformatics research and in developing good bioinformatics human resource. Two years of rigorous training in bioinformatics taught me a lot about this amazing amalgamation of biological sciences and information sciences. I was introduced to different computer programming languages and resources for application development in bioinformatics. Classes in biology, computers and emphasis on their appropriate integration made me think of biology in a very different and unconventional manner. In our second semester, we had a subject Structural Biology and Molecular Modeling (SBMM), where we were introduced to bio-macromolecular structures with a computational and biophysical perspective. With the study for this particular course, I became more focused on my area of interest. Studies of structural biology of proteins were really an interesting part of my curriculum. Eminent scientists from different national research institutes gave us insights into the structural biology of different biomolecules. I cannot go without mentioning names of some of my teachers, Prof Ashok Kolaskar (consultant, OHSL, USA and advisor, Internet2), Dr. Dhananjay Bhattacharyya (Saha Institute of Nuclear Physics), Dr. Raja Banerjee (West Bengal University of Technology), Dr. Uddhavesh Sonawane (C-DAC), Prof P. V. Balaji (IIT, Mumbai) to name a few.

My first research experience in the field of Bioinformatics was my master's degree research project under the guidance Dr. Pramod Wangikar in his Bio-systems Engineering Laboratory at Chemical Engineering department of Indian Institute of Technology (IIT), Mumbai. Though it was not directly connected to my area of interest, it gave me insights into how research methodology works for computational biology. Here I worked with analysis of regulatory elements of cyanobacteria- Synechocystis as a small part of large systems biology project going on in his lab. This project, as a whole, was aiming towards building a systemic model of Synechocystis. My contribution was to utilize microarray data for gene expression of all Synechocystis genes and transcription factor binding site analysis in order to annotate some of the genes. I could predict the function of two genes which found to be related to photosynthetic pathway but were unknown till date. I got familiar with the real life applications of different tools and techniques that I had studied before. From here, I determined to pursue my career in the research field and contribute as per my capabilities to the scientific community.

After MSc, I worked under the guidance of Prof Valadi Jayaraman from Center for Development of Advanced Computing (C-DAC), India. I worked with Prof Jayaraman on short term project titled Prediction of RNA binding proteins using random forests. His excellent guidance and my hard work contributed to my understanding of machine learning applications in biology and utilizing information from biological structures for better understanding of the biological processes. The project involved extraction of important features from the RNA binding domain of many RNA binding proteins and training the random forest classifier to make accurate predictions about RNA binding properties of unknown proteins. This again provided me with a very useful technique of machine learning for solving problems in biology and also enhanced my skills of computer programming for real life applications.

Parallel to this work with Prof Jayaraman, I also worked in an industry, Persistent Systems Limited, Pune as Domain Analyst, where I learnt a lot about industrial perspective of bioinformatics and recent IT advancements helping bioinformatics grow. It gave me an opportunity to organize my thoughts, represent myself professionally and to learn time and resource management. I worked on providing training and support to many of US universities, our clients, for caTissue clinical informatics application. But my passion and determination for doing research prepared my mind to leave industry and carry out research.

I applied for the post of Research Associate at Bioinformatics Centre, University of Pune. I got selected after rigorous interview process by an elegant panel under the Centre of Excellence (CoE) grant of Dept. of Biotechnology (DBT), Govt. of India. Here I started working on some of the government funded projects. I worked on "Understanding the mechanism of anisomycin induced activation of p38 MAP kinase using computational approach" under the eminent guidance of Dr. Sangeeta Sawant. Anisomycin is an antibiotic, which also activates p38 MAP kinase, an important component of signal transduction. But no information is available on how exactly it binds to and activates p38 MAP kinase. I attempted to perform molecular docking studies and molecular dynamics simulation experiments. This work resulted in finding out putative binding site for anisomycin on p38 MAPK and in understanding different molecular interactions taking place at the interface of these two molecules. I learnt a lot about structural properties of proteins and power of MD Simulations to explore mechanisms underlying cellular processes. I used Amber molecular dynamics simulation package extensively to carry out the simulations. Another project was "Studying the relative stabilities of conformational epitopes: a case study of lysozyme", which was carried out under the guidance of Dr. Sangeeta Sawant and Dr. Urmila Kulkarni-Kale. This study was carried out to understand the relative stabilities of individual epitopes and finding out epitopes which might retain their stability during their processing. We could support the hypothesis that such epitopes do exist and can be identified. Possible application of this study would be in identifying potential drug/vaccine targets. We used unfolding simulation technique to study the phenomenon. I am happy to state that a part of this work was presented with lot of appreciation at International Conference on Biomolecular Forms and Functions, held at Indian Institute of Science, Bangalore and complete work is in final stages of its submission for publication. Both these projects equipped me with a required attitude to carry out research and think in a logical and rational fashion to come to a solution. It made my foundations about structural biology, biophysical chemistry and computer simulations stronger than they were. Currently I am holding the same position and trying to take my work to a logical end.

Currently, I am also involved in the development of Chemical Reaction Optimization (CRO) based gene selection algorithm under the guidance of Prof Valadi Jayaraman of C-DAC, Pune. This project work, which had just started, is utilizing my programming and bioinformatics skills to design and implement gene selection algorithm using CRO, a recently proposed optimization technique.

I also served as a visiting faculty of bioinformatics for biotechnology students at Ruia College, Mumbai, which prepared me for my domain subject with more responsibilities. It helped me to become more confident and responsible to make others understand bioinformatics in a subtle manner. Teaching microarray data analysis at University of Pune, Pune and Patkar College, Mumbai also helped my teaching skills grow. I also organized and conducted a four day workshop on bioinformatics for biologists at Ruia College. Success of this workshop and positive response from the participant made me confident about my organizational skills. I have attended large number of conferences and workshops, have presented my work at national level conferences thus have had constant updates about new realm of biological research. I also appeared for BioInformatics National Certification (BINC) examination, conducted by Dept. of Biotechnology (DBT), Govt. of India, to test the ability of bioinformatics human resource and certify and felicitate very few of them who deserve to be good bioinformaticians. This exam is important in way that it holds three papers, two usual objective and theory questions which test your subject knowledge and one practical session which examines your ability to write computer programs for bioinformatics. I was awarded BINC certification with All India Rank (AIR) 14 and also a fellowship to pursue further research in the field. BINC certification boosted my confidence about my knowledge of bioinformatics. I also have received appreciation from faculty for good computer programming and currently I am involved in development of a program suit for integrating phylogenetic analysis software tools to prepare an automated pipeline.

Proteins, essential biomolecules, are the workhorses of all the cellular functions. Their characteristics and functions are mainly attributed to their tertiary structure. Always amazed by the way this machinery works; I am interested to work on structural bioinformatics of proteins and their interactions with other molecules. My primary research interests continue to be in the development of novel methodologies to understand mechanisms underlying cellular processes. There are many other research areas in structural biology which interest me like molecular modeling and molecular dynamics simulation, algorithm development and implementations, protein structure evolution, understanding the protein-protein interactions, prediction of protein structure all of which are interlinked in a way or other.

I have been introduced to protein structure by eminent panel of scientists working in this area, and that has elevated my interests to a greater height and inspired me to pursue research in the same. My year long research experience in the field of molecular dynamics simulations and molecular docking, in order to understand the mechanisms of biological processes and for facilitating vaccine development have given me required experience. Also, it introduced me to some of the limitations and requirements of existing methods of protein structure analysis. One of my research interests is to come up with a newer representation of protein structure for use in molecular dynamics simulation. Currently available methods require really exhaustive computation power as it involves enormous calculations on each and every atom of the system. It takes huge amount of time on simple machines to run a molecular dynamics simulation. While working with various simulations, I have observed that implicit solvent models can be good target to achieve this goal. There is a need to improve these models in such a way that they will approximate explicit solvent simulations in a better way. One of the ways in which it might work is deriving patterns of interactions from explicit solvent systems and incorporating them in implicit solvent models. Current implicit solvent models include theoretical effect of solvent molecules but we could improve these models by introducing not only distance dependence, but also time dependent solvent interactions. It means that we could introduce effect of actual solvent system at specific time intervals by adding some solvent molecules and redefine the model after each interval thus propagating the changes brought about by solvent molecules.

Another research area which appeals me most is protein structure prediction. Looking back in the history of bioinformatics, enormous efforts have been taken to understand and predict protein structure, which in turn imparts function to the protein. Our limited success even after such enormous efforts illustrates why protein structure prediction is known as Holy Grail of bioinformatics. Though I have had no experience in the area, I find it very interesting area to work upon and utilize my knowledge of protein chemistry, machine learning and computer programming and algorithms to contribute to the field.

As we look at the important milestones in the history of computer science, we can see distinct markings in the development of artificial intelligence. On one hand, biology is exploring expertise from various disciplines to be utilized in biological research and on the other hand, techniques in computer science have ever since widened their applicability domain. With this, my profound interest in computers and my passion for biology has widened my research goals to applications of machine learning techniques in bioinformatics and computational biology. I have strong experience in using support vector machines and random forest classifiers for solving simple biological problems and I wish to go further and help solve much more complex problems using machine learning. Currently I am involved in the development of chemical reaction optimization (CRO) based gene selection algorithm. My primary interest in this area is predicting accurate ligand binding sites on a protein structure. Current ligand binding site prediction algorithms work on quite generalized principles like geometry based, energy based etc. I strongly think that protein cavity detection for proper ligand binding should be based on more empirical principles and knowledge should be brought in from large number of known protein cavities and ligands. Classification of proteins and ligand into several classes and characterizing each class on certain properties seems essential to me before applying any generalized ligand binding site prediction algorithm.

Another aspect that I would like to explore is protein folding and dynamics. Most of the efforts we have made understand an essential process of protein folding attribute it to the inherent properties of proteins, but many of the experimental results have shown that many other factors in the cell contribute to the protein folding process. Chaperons, microenvironment, different ions also play a role. I would like to go a step further and try to gather all these factors together in a computational paradigm and try understand folding in better manner. Folding of a protein, which is crucial step in determining its functions and interactions, will help in developing new drug targets and treatments for various diseases.

These are some of the problems I would like to work upon. My long time career goals are to establish myself as a researcher in the field of protein science and contribute as per my capabilities to the society. I also want to be constantly indulged in teaching biology, as I really enjoy teaching and sharing my knowledge. Also it makes me more confident with the subject I teach.

With my training and experiences, and my research and career goals, I need a suitable place where I can utilize my knowledge and experience to develop my ideas further and put them to people's use. While searching for such environment, I was particularly attracted by a very novel program in Mathematical, Computational and Systems Biology at University of California, Irvine. Amazing blend of excellent researchers from various disciplines would surely make a difference. That's why I decided to apply at UCI. I am particularly interested in the work of Ray Luo.