John A. Hanover, Ph.D.
The Cell Biochemistry Section employs diverse genetic and biochemical tools to understand mechanisms of nutrient sensing and nuclear-cytoplasmic regulation. Researchers are interested in organelle biogenesis, innate immunity, and developmental plasticity. The central focus of the Section is understanding how nutrient availability may influence disease susceptibility in the current population through transgenerational epigenetic influences such as O-GlcNAc cycling.
Cell Cycle Regulation and Nuclear Structure Section
Orna Cohen-Fix, Ph.D.
The Cell Cycle Regulation and Nuclear Structure Section focuses on cell cycle regulation and nuclear architecture. Researchers primarily conduct cell cycle studies in budding yeast. This experimental system allows scientists to combine genetic, biochemical, cytological, and molecular biology methodologies easily and effectively.
Gene Expression and Regulation Section
Deborah M. Hinton, Ph.D.
The Gene Expression and Regulation Section investigates the mechanisms of transcription initiation and activation using a simple model system based on bacteriophage T4 gene expression. The action of transcriptional activators and coactivators often regulates transcription, which is critical for normal development.
Gene Structure and Disease Section
Karen Usdin, Ph.D.
The Gene Structure and Disease Section is interested in understanding the relationship between mutation and disease pathology in genetic disorders where the mutation occurs outside of the open reading frame, and thus where the consequences of the mutation are not immediately obvious. In particular we are interested in understanding the molecular basis of the unusual mutation that is responsible for the Fragile X-related disorders (FXDs) and the unusual consequences of this mutation for human health.
Genomic Structure and Function Section
Anthony V. Furano, M.D.
This section is concerned with two issues that are determinative of genomic structure and function: (1) We employ evolutionary, biochemical and allied techniques to determine the properties of the mammalian non-LTR L1 (LINE-1) retrotransposon, a persistent, continually evolving, intra-genomic parasite that has by now generated over 50% of its host's DNA. (2) We use bioinformatic and experimental methods to determine the factors that affect the mutation rate, with a focus on the mechanisms whereby DNA repair induces mutations in normal flanking DNA. We have experimentally verified the latter mechanism with a model system that we use to determine the factors involved in repair-induced mutagenesis.
Lipid Trafficking and Organelle Biogenesis Section
William Prinz, Ph.D.
The Lipid Trafficking and Organelle Biogenesis Section studies different aspects of organelle biogenesis in the model organism S. cerevisiae. In this work, researchers use a combination of biochemical, genetic, and imaging approaches. Specific projects include investigations of intracellular lipid trafficking, phospholipid trafficking to mitochondria and peroxisomes, and understanding the proteins that determine endoplasmic reticulum (ER) structure.
RNA Biology Section
Astrid D. Haase, M.D., Ph.D., Stadtman Tenure Track Investigator
The RNA Biology Section studies the function of small non-coding RNAs in genome surveillance. A particular class of small RNAs, PIWI-interacting RNAs (piRNAs), silence mobile genetic elements in germ cells and thus guard genomic integrity and ensure fertility in animals. Combining Drosophila genetics, biochemistry and next-generation sequencing our research aims to elucidate mechanisms of piRNA silencing and to further our understanding of fundamental mechanisms that survey and guard genomic integrity.
Structural Cell Biology Section
Jenny E. Hinshaw, Ph.D.
The Structural Cell Biology Section studies membrane and protein recycling within eukaryotic cells. Researchers examine the structure and function of proteins involved in these processes by transmission electron microscopy, including cyro-electron microscopy, and by biochemical methods. Presently, Section scientists are investigating a 100 kDa GTPase called dynamin. Dynamin is involved in the constriction and fission of clathrin-coated pits from plasma membrane during receptor-mediated endocytosis and during membrane retrieval in nerve terminals. Researchers in the Section have shown that dynamin self-assembles into spirals and onto lipid bilayers to form dynamin decorated lipid tubes. These tubes undergo a large conformational change upon GTP addition, which results in membrane constriction. To understand further the mechanism of dynamin-induced membrane constriction, staff members have solved the 3-dimensional structure of dynamin in the non-constricted and constricted states by high-resolution electron microscopy and image processing methods. This work suggests a GTP-induced conformational change within the dynamin oligomer is responsible for constriction. Additional dynamin family members are implicated in numerous fundamental cellular processes, including other membrane fission events, anti-viral activity, cell plate formation, and chloroplast biogenesis. Current work examines the effects of GTP on these proteins to determine if a common mechanism of action exists for all dynamin family members.