GOALS OF THE CENTER
Although representing diverse biological systems, an essential aspect of research in the Center for Molecular Genetics is the use of in vitro genetic research tools to explore fundamental aspects of the structure, expression and regulation of the genetic material. Participation in Center activities provides faculty, postdoctoral research associates, and graduate students with state-of-the-art research tools through shared core facilities (such as automated DNA sequencers and synthesizers). Collaboration between Center members and other molecular biologists in the region is facilitated by a series of seminars and research conferences. These include an annual conference on novel aspects of molecular biology or genetics that has attracted international acclaim. The research activities of Center faculty,conducted on organisms ranging from bacteria to primates, has an excellent record of external funding from Federal agencies such as the National Institutes of Health and the National Science Foundation.
Postdoctoral Research Associates
Administration of Annual Conferences
Dmitry Belostotsky, assistant professor;firstname.lastname@example.org
We are investigating how plant gene expression is regulated at posttranscriptional level. Specifically, we are studying poly(A)binding proteins (PABPs) in the model plant Arabidopsis thaliana.We are also using yeast as a heterologous model in which molecular aspects of plant PABPs action can be tested. Although PABP is essential for viability in yeast and is thought to increase translational initiation and initiate RNA turnover, little is known about the mechanisms involved, particularly in higher eukaryotes. We have demonstrated that small genome of Arabidopsis contains large and divergent multigene family encoding PABPs, and that individual PABP genes are under unique developmental control. One of the genes, expressed exclusively in reproductive tissues, complements PABP-deficient yeast, demonstrating that basic PABP-dependent pathways of mRNA turnover and translational initiation have been conserved in evolution.Current work is directed towards the elucidation of the functions of individual PABP genes, particularly those expressed in reproductive organs of Arabidopsis.
Richard P. Cunningham, professor; email@example.com
My laboratory is working on DNA repair mechanisms and DNA repair enzymes. We are using a concerted program of structural analysis, biochemistry and genetics to understand how organisms respond to DNA damage caused by environmental factors, as well as endogenous processes that produce genotoxic compounds. We have chosen E. coli as a model system and are studying a number of enzymes and genes involved in base excision repair. Structural studies complemented by site-directed mutagenesis are being used to probe enzyme mechanisms. Genetic studies are focused on the regulation of DNA repair genes in response to environmental stress. Since DNA repair enzymes are highly conserved throughout nature, these studies are highly relevant to processes in eucaryotes including aging and carcinogenesis.
Niles Lehman, assistant professor;
My research centers around the concepts of population genetics and molecular evolution. In a general sense I aminterested in how populations of related genotypes alter their compositions in both space and time, and in thenature of the genetic "glue" that keeps these sets of genotypes tied together as a cohesive evolutionary unit.Specifically, I and members of my laboratory are using molecular markers to study natural populations oforganisms including Daphnia (a freshwater microcrustacean), pinnipeds, canids, and other species. In Daphnia weare concerned with the speciation problem, and we are trying to uncover the patterns of gene flow that unite ordifferentiate populations in discrete lakes and ponds. In seals we are concerned with population persistence, andwe are focusing on natural variation in immunologically-relavant loci as a potential indicator of a population'sgenetic status. A second line of research in my lab utilizes the recently developed molecular technique of in vitroevolution that exploits the catalytic properties of some RNA molecules. The goal of these experiments is to be ableto describe the progress of a diverse pool of RNA sequences as it migrates through sequence space under definedevolutionary pressures.
Joseph P. Mascarenhas, professor,
The laboratory is interested in the regulation of gene activity during differentiation in plants with a special interest in the development of the male and female gametes. Several genes expressed during male and female development have been isolated. Transgenic plants have been constructed with a view to identifying the functions of several of the isolated genes in male gametophyte development. We have recently discovered retroelements that are transcribed in early microspores in maize. The potential importance of retroelements in genome evolution and male gametophyte development are being studied.
Robert Osuna, assistant professor;
The understanding of how specific interactions between a DNA binding protein and DNA can affect various DNA functions is of fundamental importance in molecular biology. This laboratory focuses on the study of the DNA-binding and -bending protein Fis (Factor for Inversion Stimulation) in E. coli. We wish to understand: 1) how Fis protein interacts with DNA and other proteins to modify gene expression, 2) how the expression of Fis itself (which displays an unusual pattern of regulation) is regulated in the cell, and 3) what novel genes are being regulated by Fis. A variety of genetic and biochemical approaches will be used to gain insight into these processes both in vivo and in vitro.
David Shub, professor;
Our lab studies the origin and function of self-splicing introns in bacteria.
1. Origin: RNA splicing has been described as already existing in a prebiotic RNA World or, alternatively, as a relatively recent addition to the genetic apparatus. We are attempting to resolve this controversy by tracing the evolutionary history of self-splicing introns in diverse lineages of bacteria and bacterial viruses. 2. Function: Thepersistence of introns in the compact genomes of bacteria and their viruses suggests that they have a selective value. We are exploring the possibility that splicing is inhibited under certain conditions of growth and that regulation of splicing may be used to regulate gene expression. Techniques employed in these studies include genome analysis by PCR and DNA probes, in vitro mutagenesis, gene fusions, and functional assays for RNA splicing in vivo and in vitro.
Caro-Beth Stewart, associate professor; firstname.lastname@example.org
The research in my laboratory is aimed at understanding the molecular basis for adaptive evolution in complex organisms. Currently, our major project focuses on the molecular mechanisms underlying the independent evolution of foregut fermentation in the ruminants and leaf-eating colobine monkeys. Specifically, we are studying the sequence and functional evolution of two enzymes, stomach lysozyme and pancreatic ribonuclease, which help these mammalian species digest the foregut bacteria. As a framework for these comparative studies we are determining the molecular phylogeny of the colobine monkeys by sequencing and analyzing appropriate mitochondrial and nuclear genes. Future studies on this project will include in vitro analysis of lysozyme and ribonuclease gene expression, as well as site-specific mutagenesis of these gene products.
Richard S. Zitomer, professor;
Our research focuses on the mechanisms by which the model eucaryote yeast regulates the expression of its genes in response to oxygen. There are at least three distinct sets of oxygen regulated genes. The first includes a large number of nuclear genes that encode mitochondrial functions involved in respiration; transcription of this set is activated in the presence of oxygen. The second set includes a number of alternate respiratory functions; transcription of these genes is repressed in high oxygen levels. We combine classical yeast genetics and current molecular techniques to identify and clone the regulatory genes and to study the target DNA sequences with which they interact.