Research in Bioinformatics
Bioinformatics is an interdisciplinary field that intersects the study of biology, computer science, chemistry, and applied mathematics. Advanced computational skills allow scientists to manage, process, and understand large amounts of biological data. While the bioinformatics program may be new at Franklin & Marshall College, the faculty has been using tools and analysis for bioinformatics over 13 years.
Bioinformatics at Franklin & Marshall College is classified into five categories:
Proteomics: the study of proteins
Medical Genomics: applying bioinformatic tools to medicine
Integrative Bioinformatics Research: field experimentation combined with bioinformatic tools
Computational Biology: using computer science and mathematics to investigate biological problems
Genomics: the study of genes
Jaime Blair (Biology): Research in Professor Blair's lab focuses on the use of genomic data and bioinformatics tools to understand the evolution of plant pathogens, specifically the fungus-like Oomycetes. A combination of computational and experimental approaches are used to explore evolutionary relationships among different types of plant pathogens, and to investigate the role of specific genomic elements associated with host specificity, virulence, and speciation.
Pablo Jenik (Biology): Professor Jenik researches the connections between gene regulation at several levels, cell identity, and tissue patterning during the development in the mustard weed Arabidopsis thaliana. His work involves characterizing mutant phenotypes, finding which gene has been mutated and then, using genetic and molecular approaches, understanding how the products of those genes regulate development.
Proteomics: the study of proteins
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Peter Fields (Biology): Professor Fields' research interests focus on adaptations to extreme environments at the biochemical and molecular levels. His past research focused on rates and types of changes in enzymes from organisms adapted to extreme cold (Antarctic fishes) or heat (Galápagos marine iguanas). Currently, his lab is pursuing research in rapid acclimation to environmental stresses such as heat shock, by measuring resultant changes in small molecular weight compounds (osmolytes, metabolites) in marine invertebrates. This work involves the use of high-pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) to measure changes in the concentration of specific compounds, as well as to identify those compounds in tissue extracts. In addition, the Fields lab is beginning to use proteomics techniques to examine changes in protein expression levels in intertidal organisms after heat stress. This work involves the use of two-dimensional gel electrophoresis, digital gel analysis and comparison, and protein identification via MS.
Ryan Mehl (Chemistry): Professor Mehl's research interests focus on the use of unnatural amino to study protein interactions and dynamics both in vivo and in vitro. Genetic incorporation of unnatural amino acids provides precise, site-specific control over a wide variety of chemical structures new to protein chemistry. In order to engineer organisms that can build proteins with unnatural amino acids, we need to build and screen large genetic libraries. Assessing the function of the evolved translational machinery involves comparing many new protein sequences with their ability to work with amino acid libraries. Understanding the functional properties of the new translational machinery allows us to greater predictive control over the incorporation of new and useful unnatural amino acids.
In a very different research project, Professor Mehl is working with Professor Ken Hess, F&M professor of Analytical Chemistry, and the Clinic for Special Children, a local specialized clinic that provides comprehensive medical care for Amish and Mennonite children with genetic disorders. Proteomics research by the Clinic for Special Children has revealed an untreatable genetic disorder in the Amish community, GM3 synthase deficiency. This GM3 synthase deficiency prevents synthesis of complex gangliosides in newborn's brains resulting in arrested brain growth and eventually death. The GM3 research project aims to advanced techniques for monitoring GM3 levels from biological samples and develop an effective treatment for the GM3 synthase deficiency disorder.
Robert Jinks (Biology): Professor Jinks investigates how the brain regulates the daily metabolism of the retina using the horseshoe crab Limulus as a simple model system. Each day rod photoreceptors in our retinas shed and renew a portion of the light sensitive membrane of their outer segments. In humans, this process is regulated by the circadian clock, and triggered by light. This daily renewal is vital for healthy normal vision. Photoreceptors in the horseshoe crab retina also undergo daily shedding and renewal of a portion of their light-sensitive membrane; here again, the process is regulated by the circadian clock and triggered by dawn.
Professor Jinks has determined (1) the metabotrophic signaling cascade that the circadian clock uses to prime the photoreceptors for daily shredding and renewal, and (2) the signaling cascade through which light triggers shedding. We are now using proteomic and bioinformatics techniques and tools to probe the point(s) of convergence of these two signaling cascades. From the bioinformatics perspective, we are designing small-interfering RNAs (siRNAs) that we can microinject directly into photoreceptor cells to disrupt the translation of key proteins that may serve as targets for the clock and light in driving daily shedding and renewal of the light-sensitive membrane. Knocking down (reducing the abundance) of these proteins with the siRNAs provides us an opportunity to study the roles of these proteins in normal retinal metabolism.
Medical Genomics: applying bioinformatic tools to medicine
Erik Puffenberger (The Clinic for Special Children): Dr. Puffenberger is the Laboratory Director at the Clinic for Special Children in Strasburg, PA. The clinic manages the care of children with a variety of metabolic and genetic disorders; eighty-five percent of the clinic patients are from the Plain sects (Amish and Mennonite). The clinic laboratory has strived to utilize the explosion of molecular genetic information in the clinical setting. We have initiated a research program designed to identify mutations in candidate genes, to develop genetic testing for rapid diagnosis and newborn screening, and to map and identify novel disease-related genes. The clinic views the genetic testing we perform as fundamentally no different than the routine testing that is used commonly in clinical practice. Our ability to rapidly and efficiently use molecular genetic techniques to answer difficult questions has resulted in decreased healthcare costs for the Plain community, increased the efficiency and speed of diagnosis, and improved treatment and management of genetic diseases. Student research projects have involved implementation of modern molecular genetic techniques for routine disease diagnosis, research into the genetics of isolated populations, development of strategies for newborn screening, and identification of novel disease genes by linkage mapping.
Holmes Morton and Kevin Strauss (The Clinic for Special Children): Drs. Morton and Strauss are both pediatricians at The Clinic for Special Children. Their work is aimed at preventing disability and untimely death in children with genetic disorders. Dr. Strauss has a special interest in brain development and how it is affected by genetic disorders. Dr. Strauss' published work explores the complex interplay among gene mutations, environment, and tissue injury in the clinical setting. These studies provide a foundation for developing new approaches to treatment and prevention.
Integrative Bioinformatics Research: field experimentation combined with bioinformatic tools
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niel Ardia (Biology): Professor Ardia uses statistical tools to test hypotheses about life history evolution, using large data sets relating to the evolutionary, population and physiological ecology of birds and insects.
Jorge Mena-Ali (Biology): Research in Jorge Mena-Ali's lab is centered on the evolution and ecology or reproductive strategies in plants, especially as it relates to invasive species and the conservation of endangered species. In their research projects students apply and integrate population, genomic, molecular and quantitative genetic tools and techniques to understand the ecological dynamics of invasive species, and the evolutionary consequences of new habitats on their reproductive strategies and life history.
Kathleen Triman (Biology): Professor Triman has developed and maintained a Ribosomal RNA Mutation Database and has published 3 major tabulations of the database in Advances in Genetics.
Computational Biology: using computer science and mathematics to investigate biological problems
Professor Jing Hu (Mathematics): Professor Jing Hu's primary research goal is to develop and apply computationally intensive techniques such as data mining and machine learning algorithms to address challenges in understanding biological systems. This approach involves theories and techniques from multi-disciplinary fields of computer science, statistics, biochemistry and biophysics. Jing Hu's generalized research workflow is to identify and study biological problems, construct computational models, develop and apply efficient and effective machine learning techniques to systematically analyze and understand biological processes. Specifically, Jing Hu's recent research focuses on problems such as prediction of protein structures, functions and functional sites, and identification of deleterious nsSNPs.
Professor Christina Weaver (Mathematics): Professor Weaver develops mathematical models and techniques to analyze how properties describing the shape and excitability of a neuron's dendrites interact to affect its function. These properties vary during development, learning, aging and disease. Professor Weaver's research aims to predict which of these properties should be changed to counteract problems that interrupt normal function. Such predictions might one day contribute to effective therapies for many neural disorders and brain injuries.
