Department: Structural Biology

Axel Brunger's goal is to understand the molecular mechanism of synaptic neurotransmission. He is particularly interested in the structure, function, and dynamics of key players in the synaptic vesicle fusion machinery. His lab is also working on the mechanism of action of clostridial neurotoxins that target this machinery. A molecular understanding of these complex protein machineries may ultimately lead to new therapeutics to treat human diseases.

Molecular motors lie at the heart of biological processes from DNA replication to vesicle transport. My laboratory seeks to understand the physical mechanisms by which these nanoscale machines convert chemical energy into mechanical work.

I am not now actively involved in research, but my past endeavors remain central to my position in guiding medical students in their scholarship pursuits. The cited publications represent three areas of interest: (1) medical student research (Jacobs and Cross) (2) women in medicine (Cross and Steward) (3) the reproductive physiology of early development (Cross and Brinster) Only one publication is listed in this area since the research is not current, but others (in e.g. Nature, DevBiol, ..

Structural and functional studies of transmembrane receptor interactions with their ligands in systems relevant to human health and disease - primarily in immunity, infection, and neurobiology. We study these problems using protein engineering, structural, biochemical, and combinatorial biology approaches.

The Jardetzky laboratory is studying the structures and mechanisms of macromolecular complexes important in viral pathogenesis, allergic hypersensitivities and the regulation of cellular growth and differentiation, with an interest in uncovering novel conceptual approaches to intervening in disease processes. Ongoing research projects include studies of paramyxovirus and herpesvirus entry mechanisms, IgE-receptor structure and function and TGF-beta ligand signaling pathways.

We study the regulation of transcription, the first step in gene expression. The main lines of our work are 1) reconstitution of the process with more than 50 pure proteins and mechanistic analysis, 2) structure determination of the 50 protein complex at atomic resolution, and 3) studies of chromatin remodelling, required for transcription of the DNA template in living cells

having pioneered, we (a) predict folding of a polypeptide and RNA chains into a unique native-structure, we (b) model protein structure using the well-established paradigms that similar protein sequences imply similar three-dimensional structures, and (c) we are focusing on mesoscale modeling of large macromolecular complexes such as RNA polymerase and the mammalian chaperonin.

Three-dimensional structure determination and biophysical studies of macromolecules.

The central theme of our research is to develop and apply novel theoretical methods to understand the physical properties of biological molecules, such as proteins, nucleic acids, lipid membranes, and small molecule therapeutics (eg protein folding or lipid vesicle fusion). As these phenomena are complex, my research employs novel theoretical and computational techniques. We apply these methods to develop novel therapeutics for protein misfolding diseases, such as Alzheimer's Disease.

The Parham laboratory investigates the biology, genetics, and evolution of MHC class I molecules and NK cell receptors.

The Puglisi group investigates the role of RNA in cellular processes and disease. We investigate dynamics using single-molecule approaches. Our goal is a unified picture of structure, dynamics and function. We are currently focused on the mechanism and regulation of translation, and the role of RNA in viral infections. A long-term goal is to target processes involving RNA with novel therapeutic strategies.

Viral infections and subsequent host response depend on multiple RNA-protein interaction. My research focuses on the structural and functional characterization of RNA-protein complexes involved in viral infection. Current research aims to understand how the Human Immunodeficiency Virus (HIV) initiates its replication upon host infection. We use NMR spectroscopy and x-ray crystallography to study the structure of the initiation complex, formed by a host tRNA and HIV genomic RNA, coupled with bio..

Our laboratory studies molecular interactions that underlie the establishment and maintenance of cell and tissue structure. Our specific areas of interest are the architecture and dynamics of intercellular adhesion junctions, the molecular basis of cell polarity, and the Wnt signaling pathway. We also have a long-standing interest in carbohydrate-based cellular recognition and adhesion.