My research focuses on developing biologically based models for the uptake, distribution, metabolism, and biological effects of drugs and chemicals and their application to safety assessments and quantitative health risk assessments. In recent years, my research emphasis has been on developing mathematical descriptions of control of genetic circuitry and the dose-response and risk-assessment implications of these control processes.
We study interactions of proteins and peptides with membranes. Specifically we study the interaction of the A-beta peptide with lipids in the membrane. It is well known that Alzheimer’s is an aggregation disorder with A-beta being the aggregating species. However, it is unknown what initiates this aggregation. Experimental evidence has shown that A-beta peptides will undergo a conformational change to an aggregate structure when interacting with surfaces of certain lipid membranes. It is of interest to our group to understand what causes this conformational change and what properties of lipids most promote this effect.
We also study structural and dynamical properties of biomembranes containing cholesterol. The goal of our research on structural and dynamical properties of membranes containing cholesterol is to gain knowledge about the nature of phospholipid-cholesterol interactions that play an important role in functioning of membranes, in cell communications and in formation of domains called lipid rafts. Detailed knowledge of the membrane properties helps us to understand the normal functioning of cells and it is instrumental in the search for a cure from a large variety of diseases. We use computer simulation techniques to perform our studies. Member of the Molecular & Cellular Biophysics Training Program
Experimental Evolution of Viruses. We use both computational and experimental approaches to understand how viruses adapt to their host environment. Our research attempts to determine how genome complexity constrains adaptation, and how virus ecology and genetics interact to determine whether a virus will shift to utilizing new host. In addition, we are trying to develop a framework for predicting which virus genes will contribute to adaptation in particular ecological scenarios such as frequent co-infection of hosts by multiple virus strains. For more information, and for advice on applying to graduate school at UNC, check out my lab website www.unc.edu/~cburch/lab.
Molecular evolution and mechanistic enzymology find powerful synergy in our study of aminoacyl-tRNA synthetases, which translate the genetic code. Class I Tryptophanyl-tRNA Synthetase stores free energy as conformational strain imposed by long-range, interactions on the minimal catalytic domain (MCD) when it binds ATP. We study how this allostery works using X-ray crystallography, bioinformatics, molecular dynamics, enzyme kinetics, and thermodynamics. As coding sequences for class I and II MCDs have significant complementarity, we also pursuing their sense/antisense ancestry. Member of the Molecular & Cellular Biophysics Training Program.
Developing and applying novel mass spectrometry (MS)-based proteomics methodologies for high throughput identification, quantification, and characterization of the pathologically relevant changes in protein expression, post-translational modifications (PTMs), and protein-protein interactions. Focuses in the lab include: 1) technology development for comprehensive and quantitative proteomic analysis, 2) investigation of systems regulation in toll-like receptor-mediated pathogenesis and 3) proteomic-based mechanistic investigation of stress-induced cellular responses/effects in cancer pathogenesis.
Our laboratory has research interests that include developmental neurotoxicity, with an emphasis on the use of mode-of-action models to study the impact of endocrine disruptors and the cumulative risk of thyroid disruptors and pesticides.
My interests focus on developing quantiative methods to assess the relationships between exposure, dose and response. This research has examined methods for dioxins, thyroid hormone disruptors and pyrethroid pesticides.
The Dokholyan group focuses primarily on understanding protein dynamics, more specifically on how induced changes in protein folding and aggregation lead to diseases, such as cystic fibrosis, many types of cancers, and a number of neurodegenerative diseases. The Dokholyan group focuses on several such diseases, including Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, and Huntington disease. The Dokholyan group is developing a hierarchy of molecular models, from simplified coarse-grained models to more detailed ones, to create a novel multi-scale simulation methodology. This methodology will enable simulations of large molecular complexes at the biologically-relevant time scales, thereby allowing to directly glance into processes associated with human diseases. Member of the Molecular & Cellular Biophysics Training Program.
The Elston lab is interested in understanding the dynamics of complex biological systems, and developing reliable mathematical models that capture the essential components of these systems. The projects in the lab encompass a wide variety of biological phenomena including signaling through MAPK pathways, noise in gene regulatory networks, airway surface volume regulation, and understanding energy transduction in motor proteins. A major focus of our research is understanding the role of molecular level noise in cellular and molecular processes. We have developed the software tool BioNetS to accurately and efficiently simulate stochastic models of biochemical networks
Involvement of the epidermal growth factor receptor and its ligands in development, differentiation, and carcinogenesis of the mammary gland. Signaling mechanisms of endocrine disrupting toxicants having adverse effects on mammary gland development and the ability of the gland to lactate. Mechanism of action of atrazine, simazine, and cyanazine in the brain.
Research interests include: transport processes in the lung, flow and structure of nano-materials & macromolecular fluids, weakly compressible transport phenomena, solitons and optical fiber applications, inverse problems for material characterization and modeling of transport in multiphase porous media.
Our primary research is in the area of computational systems biology, with particular interest in the study of biological signaling networks; trying to understand their structure, evolution and dynamics. In collaboration with wet lab experimentalists, we develop and apply computational models, including probabilistic graphical and multivariate methods along with more traditional engineering approaches such as system identification and control theory, to current challenges in molecular biology and medicine. Examples of recent research projects include: prediction of protein interaction networks, multivariate modeling of signal transduction networks, and development of methods for integrating large-scale genomic data sets.
The Gupta group uses statistical and computational approaches to find conserved stochastic patterns or motifs in genome sequences. They are particularly interested in using these approaches to discover gene regulatory modules and interaction networks involved in specific biological processes.
Research in my laboratory focuses on how animals produce and control movement, with a particular interest in animal flight. We use both computational and experimental techniques to examine how organismal components such as the neuromuscular and neurosensory systems interact with the external environment via mechanics and aerodynamics to produce movement that is both accurate and robust. Keywords: biomechanics, flight, avian, insect, neural control, muscle, locomotion, computational modeling
The goal of my research is to identify, clone, and characterize the evolution of genes underlying natural adaptations in order to determine the types of genes involved, how many and what types of genetic changes occurred, and the evolutionary history of these changes. Specific areas of research include: 1) Genetic analyses of adaptations and interspecific differences in Drosophila, 2) Molecular evolution and population genetics of new genes and 3) Evolutionary analysis of QTL and genomic data.
Research in the Kaufmann laboratory is concerned with determining the mechanisms whereby cell cycle checkpoints suppress human cancer development. We are focused on two checkpoints that help to stabilize the genome. The decatenation G2 checkpoint delays mitosis until daughter chromatids are sufficiently disentangled by topoisomerase II. This checkpoint is regulated by the breast cancer susceptibility gene BRCA1. The intra-S checkpoint regulates DNA synthesis by controlling the rates of replicon initiation and DNA chain elongation. This checkpoint is regulated by two proteins, Timeless and Tipin, that mediate signaling at stalled replication forks. A program project is studying how the Timeless-Tipin replication fork protection complex protects against UV-induced chromosomal damage and sunlight-induced melanoma.
We use a combination of experimental and computational methods to redesign protein-protein interactions. The potential applications for this technology include enhancing protein therapeutic and creating new tools to study signaling pathways.
We study protein structure and dynamics as they relate to protein function and energetics. We are currently using NMR spectroscopy (e.g. spin relaxation), computation, and a variety of other biophysical techniques to gain a deeper understanding of proteins at atomic level resolution. Of specific interest is the general phenomenon of long-range communication within protein structures, such as observed in allostery and conformational change. A. Lee is a member of the Molecular & Cellular Biophysics Training Program.
Our laboratory studies the mechanisms of sensory information processing in the nervous system, with an emphasis on processing in the auditory pathways. We study the role of ion channels in integration at the single cell level, short and long-term synaptic plasticity, synaptic function, and ion channel dynamics in the auditory brainstem and auditory cortex. We are also studying how different kinds of hearing loss affect central auditory function. Experimentally, we use patch clamp (current, voltage and dynamic clamp) methods in brain slices, live optical imaging of activity, a variety of biochemical and molecular methods, mice with genetic hearing loss, noise-induced hearing loss, auditory brainstem evoked response, and acoustic startle response to evaluate hearing function in animal models. The laboratory extensively utilizes quantitative experimental techniques, complemented with detailed computational modeling at the single cell and network levels to further understand the normal information processing capacity of auditory neurons, and the consequences of changes in ion channel and synaptic function after hearing loss.
My research focuses on understanding the relationship between dermal and inhalation exposure and the effect of individual genetic differences on the function of enzymes that detoxify hazardous agents and that affect the development of disease. My research group has pioneered approaches to quantitatively measure skin and inhalation exposures to toxicants; additionally, my group has developed sophisticated exposure modeling tools using mathematical and statistical principles in an effort to standardize and improve exposure and risk assessment.
We are a theoretical physical chemistry group in the Department of Chemistry at the University of North Carolina at Chapel Hill. We use advanced computational methods to study biological processes at multiple scales, from single protein functional dynamics and chromatin folding and stability to cell-level processes, such as stochastic signal transduction and regulation of cell motility.
My graduate students and I use the formalism of equilibrium thermodynamics and the tools of molecular biology and biophysics to understand how nature designs proteins.
High-performance computing: algorithms, programming languages, compilers and architectures. Scientific computing with focus on computational biology and bioinformatics. High-level programming languages and problem solving environments.
Areas of research include: network and combinatorial reliability, Steiner tree and other network design problems, polyhedral combinatorics, combinatorial listing and enumeration algorithms, and other network and combinatorial optimization problems.
Bioinformatics, Cancer Biology, Cell Biology, Chemical Biology, Computational Biology, Genomics, Molecular Medicine, Neurobiology, Pharmacology, Systems Biology, Toxicology, Translational Medicine
Our laboratory applies molecular, biochemical, genetic and genomics approaches to understanding the mechanisms of environmental agent-related organ injury and carcinogenesis. Specifically, we are interested in nuclear receptor-mediated pathways in chemical carcinogenesis, oxidative DNA damage and repair, the role that alcohol and diet play in cancer, and the genetic determinants of the susceptibility to toxicant-induced liver injury. Through a combination of in vivo animal studies and experiments that utilize cellular and molecular models, we aim to better understand why certain chemicals cause cancer or organ damage in rodents and whether humans in general, or any susceptible sub-population in particular, are at risk from similar exposures.
The primary research projects in my lab span topics from evolutionary genetics to behavioral ecology. Prior, current and future projects of mine focus on theoretical studies of speciation and reinforcement but include work on mate choice, learning and imprinting, aposematic coloration, and brood parasitism. My main goal is to use mathematical models to integrate rigorous evolutionary theory with hypotheses explaining behavioral and ecological patterns and phenomena.
My work is centered upon the characterization of the large mucin gene products and the complexes they make which are essential for the formation of the mucus gels vital for epithelial protection and function. This work is focused around the human lung where there are many human diseases including asthma, cystic fibrosis, and chronic bronchitis in which these glycoconjugates are centrally implicated. Our studies are broad ranging and seek to build up a picture of the chemistry of these complex phenotypes, the network of their interactions that constitutes a mucosal surface and the mechanisms of their biosynthesis, assembly and secretion. The laboratory is established with a wide range of methods including MALDI and ESI mass spectrometry, electron and atomic force microscopy, hydrodynamics, theoretical molecular dynamics and a variety of surface physics tools.
My primary research area is computational geometry, in which one studies the design and analysis of algorithms for geometric computation. Computational geometry finds application in problems from solid modeling, CAD/CAM, computer graphics, molecular biology, data structuring, and robotics, as well as problems from discrete geometry and topology. Most of my work involves identifying, representing, and exploiting geometric and topological information that permit efficient computation. My current focus is on applications of computational geometry in Molecular Biology and Geographic Information Systems (GIS). Examples of the former include docking and folding problems, and scoring protein structures using Delaunay tetrahedralization.
Biophysics of cortical information processing, selective attention in the mammalian visual pathway and evidence for spike patterns in cortical spike trains
The major area of our research is Biomolecular Informatics, which implies understanding relationships between molecular structures (organic or macromolecular) and their properties (activity or function). We are interested in building validated and predictive quantitative models that relate molecular structure and its biological function using statistical and machine learning approaches. We exploit these models to make verifiable predictions about putative function of untested molecules.
"Our lab uses computational and molecular tools to study the evolution of genome organization, primarily in the flowering plants. Areas of
investigation include the origin and consequences of differences in gene order within populations and between species, the evolutionary and functional diversification of gene families (phytome.org), and the application of genomics to evolutionary model organisms (mimulusevolution.org). We also are involved in a number of cyberinfrastructure initiatives through the National Evolutionary Synthesis Center (nescent.org), including work on digital scientific libraries(datadryad.org), open bioinformatic software development (e.g. gmod.org) and the application of semantic web technologies to biological data integration(phenoscape.org)."
The Wang group designs novel data models and algorithms to address fundamental computational issues in analyzing large sets of experimental data. Ongoing research projects include: 1) Classification and clustering analysis of gene-expression profiles, 2) Discovery of discriminative structural motifs in proteins and 3) Query and integration of heterogeneous databases.
To understand the general rules of splicing regulation, a.k.a. "splicing code", we study the splicing regulation in a systematic way. We also try to engineer molecules that can modulate splicing, and use them as drugs to treat splicing diseases.
Our vision is to address one of the great remaining and intractable problems in cellular and molecular biology -- that of determining comprehensive and quantitative structures for all cellular and viral RNAs. To this end, we are developing high-throughput RNA structure analysis technologies (called SHAPE) with the goal of making RNA secondary and tertiary structure analysis as straightforward, in principle, as DNA sequencing is today. We then use these tools to understand otherwise daunting problems that play pivotal roles in cellular function. Current projects include (i) RNA folding and protein assembly reactions central to the infectivity and pathogenesis of human viruses and (ii) assembly of large biomedically important ribonucleoprotein complexes inside living cells.
