Concentration in Genetics and Molecular Biology

The area of Genetics and Molecular Biology is the study of the fundamental workings of the cell, and how cells function in the context of an organism. Areas of current research in our department cover a wide range of topics such as DNA replication and repair, gene regulation through chromatin structure, cell differentiation and cell signaling during development, and interaction of virulence factors and immune cells.
Suggested Program of Study and Appropriate Courses >

Faculty mentors:

Susan Ernst
Catherine Freudenreich
Juliet Fuhrman
Kelly McLaughlin
Mitch McVey
Sergei Mirkin

Ernst Laboratory
During embryogenesis, a developmental program encoded in the genome is expressed to create a three-dimensional organism. My students and I are interested in the molecules and mechanisms that direct and regulate this process. We have concentrated on questions of very early development and cell differentiation and how the early cell lineages become established. Using sea urchin gastrulation as a model system, we study genes that code for proteins thought to be instrumental in the morphogenetic processes required to change an undifferentiated ball of cells to a gastrula with three primary germ layers, from which all the cells and organs of the embryo will arise. Endo16, a gene that is the focus of many of our current studies, encodes a protein that appears on the surface of the invaginating archenteron cells just as they initiate the dramatic morphogenetic movements of gastrulation.

Freudenreich Laboratory
The Freudenreich laboratory studies factors that regulate genome stability, using budding yeast as a model system. We are particularly interested in unstable elements in the genome. One type of unstable element is trinucleotide repeat sequences, whose expansion causes numorous human genetic diseases such as Huntington's disease, myotonic dystrophy and fragile X syndrome. We are investigating the mechanism of trinucleotide repeat expansion using yeast genetics and molecular biology. In addition, we are interested in fragile sites, areas of chromosomes that are prone to breakage. Chromosome breakage and rearrangement is a hallmark of cancer cells, and fragile sites have been implicated in the genesis of cancer. We are studying why particular sequences are prone to breakage and the cellular conditions involved.

Fuhrman Laboratory
Our laboratory is currently studying the basic biology of parasitic roundworms in the hope of devising novel strategies for controlling infection and preventing disease. We focus in particular on filarial parasites, which are responsible for causing elephantiasis and onchocerciasis, or river blindness, in humans. Filarial parasites currently infect nearly 100 million people, most of whom live in developing nations that cannot supply expensive drug cures or implement costly control plans. We have recently used a combination of immunochemical and molecular approaches to define a "virulence factor" in Brugia malayi; this factor, the enzyme chitinase, is apparently required for the parasite to develop within the mosquito. We are studying the enzyme chitinase's structure and enzymatic properties as well as its localization within the parasite. Its precise role in the mosquito is being tested using inhibitors and recombinant protein, and its developmental regulation is being examined through genomic and cDNA analyses. The laboratory is also investigating other aspects of the mosquito-parasite interaction through an analysis of specific components of the mosquito gut that determine the insect's susceptibility to infection.

McLaughlin Laboratory
The building of organs during embryogenesis constitutes one of the most fascinating, but also least understood developmental processes. Coordinated gene action directs the developmental fate of cells to assemble into complex, three-dimensional structures with characteristic shape, size, and physiological properties. The acquisition of different cell fates initiates an elaborate interplay of cell proliferation, migration, growth, differentiation and death, bringing together cellular ensembles in a precise temporal and spatial manner. The mechanisms which intrinsic and extrinsic factors use to generate cell diversity, coordinate morphogenetic cell movements, and regulate assembly of the different tissue types comprising an organ, define one of the central questions in science today. Our research seeks to discover the basic mechanisms of vertebrate organ development, repair, and regeneration. Recent advances in Developmental Biology hold great promise in many areas of human adult and child health where the discoveries of today develop into the treatments of tomorrow.

Research Summary: The primary objective of our research is to understand how functional organs are created. Although many of the mysteries of biology have been revealed over the years, the precise molecular mechanisms used by organisms to create and pattern tissues and organs remain a mystery. Our lab takes advantage of the powerful molecular developmental model system, Xenopus laevis (frog) and uses multiple approaches in order to gain a better understanding of how organs are formed including: 1) normal organ developmental processes, 2) organ remodeling, and 3) regeneration.

McVey Laboratory
In order to accurately replicate and pass on their genetic material, cells must repair DNA damage as it arises. One of the most dangerous types of DNA damage is the double-strand break. Failure to repair double-strand breaks can result in cell death by apoptosis, while inaccurate repair can be mutagenic. The importance of double-strand break repair has been highlighted by the identification of many inherited human diseases that are caused by mutation of genes involved in the repair process. For example, some cases of familial breast cancer have been linked to mutations in two genes that have known roles in break repair: BRCA1 and BRCA2.

Double-strand breaks can be repaired by two main classes of pathways: non-homologous end-joining and homologous recombination. End-joining entails processing of broken ends and subsequent ligation and is often error-prone (it can be thought of as the "duct tape" approach to repair). Homologous recombination involves using a homologous template for repair and is generally error-free. Different cell types employ these pathways (or combinations of them) to different extents during development, depending on cell cycle and developmental cues.

Our laboratory is using Drosophila melanogaster as a model system to investigate how and when these double-strand break repair pathways are used in different cell types and to characterize genes that play crucial roles in each pathway. Our research employs a variety of classical and molecular genetic approaches, including powerful assays in which we can create double-strand breaks at known sites in the genome and recover and molecularly analyze repair events. Our long-term goal is to elucidate the mechanisms by which cells "choose" the appropriate pathways to repair different types of DNA breaks.

Mirkin Laboratory
The field of research in our laboratory, broadly defined, is DNA structure and functioning.   We are primarily interested in the role of various DNA repeats in the maintenance of the genome and their effects on major genetic transactions in norm and disease. We also study complex interplay between genetic machineries, operating simultaneously at a given genomic segment, such as replication and transcription. Finally, we are fascinated by DNA conformations that differ from the canonical B-DNA. Thus, a significant part of our research is devoted to unusual DNA structures and their biological roles. These three directions of our research are principally intertwined, building the framework for better understanding of genome structure, evolution and functioning.

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