Biomolecular Structure and Biophysics
Research includes:
- Biological NMR Spectroscopy
- Computational Chemistry/Biology
- Electron Microscopy
- Energy Transduction/Electron Transfer
- Enzyme Catalysis
- Membrane Protein Structure
- Metalloprotein Structure
- Protein Dynamics
- Protein Evolution
- Protein Folding
- RNA Structure/Biochemistry
- Signaling Protein Structure
- Virus Structure
- Xray Crystallography
Training Group Mission:
The central role of biomolecular structure and biophysics in life science research provides the rationale for a program in Biomolecular Structure and Biophysics, focusing on structures of key macromolecules and the understanding of their biological roles. The training group includes expertise in a variety of physical and computational approaches used to determine three-dimensional structure, to probe biophysical properties of biomolecules, and to predict structure/function relationships. Areas of strength include X-ray crystallography, NMR spectroscopy, electron microscopy, bioinformatics, computational biology and biophysics, chemical biology, enzymology, and biofluorescence spectroscopy.
Faculty Membership
Faculty
Research Area
Protein structure and function; X-ray crystallography; metalloenzymes; biodegradation of PCBs and related compounds
Structure and function of large protein complexes; Cryo-electron microscopy.
STRUCTURE-FUNCTION OF MEMBRANE PROTEINS:
(1) Electron Transport; Cytochrome Complexes; (2) Bacterial Toxin (Colicin) Import
(1) Electron Transport; Cytochrome Complexes; (2) Bacterial Toxin (Colicin) Import
Functional role deubiquitinating enzymes in cellular pathways implicated in neurodegeneration, such as Alzheimer's disease and Parkinson's disease
Chemical and systems biology as applied to drug discovery; design, synthesis, and evaluation of small molecule modulators of protein interactions; development and application of high content cell analysis screening platforms.
Protein-DNA interactions and protein engineering of homing endonucleases
Structural basis for RNA function
Macromolecular sequences and the evolution, structure and function of molecules; databases and computational tools for functional genomics
Multidrug resistance in human cancer
method developments and applications of cryo-EM
Soil chemistry
Our lab focuses on acquiring and utilizing high throughput sequencing data (e.g. RNA-seq, ChIP-seq, ATAC-seq) to develop new computational models and biological assays to study genome regulation and human diseases, in particular immune related disorders and cancer. We are now working on the discovery and modeling of the regulatory circuitry of the non-coding genome which is essential for maintaining normal cellular physiology.
We develop computational methods for analyzing and modeling protein structures, functions, drug molecules, cryo-EM and other biomedical image data.
Biomechanics of cytoskeleton, cells and tissues; Computational modeling of biological structures
Synaptic and dendritic integration in vitro and in vivo, sensory integration, two-photon imaging, optogenetics, sub-cellular patch-clamp recordings, nanotechology, bioelectronics
Viral gene expression; virus-host interactions; pathogenesis; virus receptors and virus assembly
Development of mass spectrometry imaging for mapping lipids, metabolites, proteins in biological samples.
Coding, modeling, computing, and simulating to develop new, effective, and safe drug products.
n/a
Magnetic resonance imaging, image and signal processing,brain decoding and modeling
Structure-Function relationships of natural product biosynthetic enzymes for combinatorial biosynthesis
Quantification of cellular activation thresholds in cancer and immune cells that interact within the complex, dynamic tumor microenvironment. Measurement of the molecular impulse-response function with single molecule and single cell precision.
Cardiovascular disease is a growing problem worldwide and the leading cause of death in the United States. Phospholipase C (PLC) enzymes, in particular PLCβ and PLCε, are essential for normal cardiovascular function. These proteins generate second messengers that regulate the concentration of intracellular calcium and the activation of protein kinase C (PKC). Dysregulation of calcium levels and PKC activity can result in cardiovascular diseases and heart failure. A new direction of research being explored is to understand how PLCε also functions as a tumor suppressor in certain cancers. We use an innovative combination of X-ray crystallography, electron microscopy, small angle X-ray scattering, and atomic force microscopy to gain structural insights into phospholipase C (PLC) regulation and activation. Structure-based hypotheses are validated through functional assays and cell-based assays, and ultimately whole animal studies. Our studies will aid in the identification and development of novel chemical probes that could be used to study the roles of PLCε in disease and serve as lead compounds for new therapeutics in cardiovascular disease and cancer.
We are interested in programmed self-assembly of nucleic acids (DNA and RNA), or DNA nanotechnology. Nucleic acids are information-rich molecules. They have well-defined secondary structures (duplexes) and simple interaction rules (Watson-Crick base pairing). These chemical properties render nucleic acids to be excellent molecules for programmed self-assembly. Since 1982, a wide range of nanostructures have been constructed and find applications in biosensing, imaging, smart drug delivery, vaccine, organizing chemical reactions, plasmonic devices etc.
Cells function by carefully orchestrating communication between proteins, often via post-translational modifications (PTMs). Dr. Mattoo’s team studies PTMs carried out by the evolutionarily conserved Fic (filamentation induced by cAMP) enzyme family. Predominant amongst these PTMs is AMPylation/adenylylation, which entails breakdown of ATP to add an AMP to the target protein. Dr. Mattoo’s group has discovered roles for AMPylation in microbial pathogenesis, mammalian stress response, and neurodegeneration (Parkinson’s Disease). By manipulating AMPylation, her team aims to intercept detrimental signals to promote cellular health.
Gene-to-Lead Drug Discovery
Protein assemblies, viruses, cryo-temperature fluorescence, cryo-electron tomography.
Structural biology, membrane proteins, protein folding, protein transport across membrane, protein import and trafficking, infectious diseases, pathogenic bacteria, multi-drug resistant bacteria, Gram-negative bacterial pathogens
System-wide Investigation of protein folding, energetics, and ligand binding
Computational chemistry and biological NMR
We study the structure-spectrum relationship in cyanobacterial photosynthesis using mutagenesis and optical spectroscopy.
Magnetic resonance imaging and spectroscopy, electromagnetic modeling in tissue
The Rochet lab has a long-standing interest in neurodegenerative disorders including PD, DLB, and AD. We have adopted the approach of detailed characterization of proteins linked pathologically and/or genetically to these disorders. We aim to elucidate mechanisms of neurodegeneration relevant to both familial and more common sporadic forms of these diseases.
Entry of retroviruses and other enveloped viruses into cells; mechanism of enzymatic phosphoryl transfer
The main focus of the lab is mechanisms by which lipid-enveloped viruses (coronaviruses, filoviruses and paramyxoviruses) replicate via assembly and budding in human cells to form new virus particles.
Macromolecular structure and assembly using X-ray crystallography; membrane associated proteins; enzyme structure and function
We primarily study the molecular basis of GPCR-mediated signal transduction, principally via the techniques of X-ray crystallography and single particle electron microscopy. By determining atomic structures of signaling proteins alone and in complex with their various targets, we can provide important insights into the molecular basis of signal transduction and how diseases result from dysfunctional regulation. The lab is also interested in rational drug design and the development of biotherapeutic enzymes.
Our group creates new organic materials for applications in drug delivery and affinity capture for high-resolution cryoelectron microscopy using a design-build-test development cycle for their performance optimization. High-throughput experimentation methods are also used in our lab to select the most promising reaction conditions for executing the continuous synthesis of drug molecules in a manner that can be rapidly upscaled to support preclinical and clinical studies.
A multidisciplinary research group aiming to decipher the molecular mechanisms underlying the complex biological systems.
Mathematical biology and applied math (applications include pattern formation and self-organization, and methods include modeling, computation, and topological techniques)
1. Structures and functions of DNA G-quadruplex secondary structures. We seek to understand the molecular structures and cellular functions of the biologically relevant DNA G-quadruplexes, including those formed in the promoter regions of human oncogenes such as MYC, BCL-2, and PDGFR-b, as well as in human telomeres. 2. Protein interactions of G-quadruplexes. We work to understand the structures and cellular functions of proteins that interact with DNA G-quadruplexes, and their therapeutic targeting. 3. Targeting G-quadruplexes for anticancer drug development. DNA G-quadruplexes are emerging as a new class of cancer-specific molecular targets. We seek to discover small molecular anticancer drugs that target the DNA G-quadruplexes for oncogene suppression (e.g. MYC). We hope to combine the potency of DNA-interactive anticancer drugs with the selectivity properties of molecular-targeted approaches. 4. Structure-based rational drug design. We use structure-based rational design in combination with structural biology, biophysical, biochemical, and cellular methods for our drug development efforts. 5. Topoisomerases’ and transcription factors’ inhibitors.
Protein tyrosine phosphatases, cellular signaling mechanism, cancer biology, chemical and structural biology, drug discovery, protein structure and function.
