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BIOCHEMISTRY AND BIOPHYSICS
 
 

• Mark Akeson (BME) Control and Analysis of DNA and RNA Using Nanoscale Pores
• Hinrich Boeger (MCD) Promoter Chromatin Dynamics and Gene Expression
• Barry Bowman (MCD) Membrane Function and Calcium Regulation
• Phil Crews (Chem) Marine Natural Products as Potent Agents Against Human Disease
• Dave Deamer (BME) Biophysics of Membranes and Single Molecules
• Rebecca DuBois (BME) Structure, Function, and Engineering of Virus Proteins
• Olöf Einarsdóttir (Chem) Structure, Mechanisms, and Dynamics of Respiratory Heme-Copper Oxidases
• Ted Holman (Chem) Lipoxygenase Inhibitors as Potential Anti-Inflammatory Drugs
• Melissa Jurica (MCD) Structure and Functional Analysis of the Spliceosome
• Doug Kellogg (MCD) Control of Cell Growth and Size
• Dave Kliger (Chem) Visual Pigment and Heme Proteins, Light, and Biological Processes
• Joel Kubby (EE) Applications of Adaptive Optics for Biological Microscopy
• Scott Lokey (Chem) A Small Molecule Approach for Studying Signaling Pathways Related to Cell Motility and Cancer
• Pradip Mascharak (Chem) Delivery of Small Messenger Molecules to Biological Targets
• Glenn Millhauser (Chem) Remarkable Protein Structures ..... and Where They Go Wrong
• Karen Ottemann (METX) Bacterial Pathogens Sense and Respond to Host Environments
• Carrie Partch (Chem) Exploring the Molecular Basis for Circadian Timekeeping in Mammals
• Nader Pourmand )BME) Single Cell Analysis and Manipulation, Biosensor, Nanotechnology, DNA Sequencing
• Jevgenij Raskatov (Chem) Disease-Oriented Chemical Biology
• Seth Rubin (Chem) Molecular Mechanisms of Cell Cycle Regulation and Cancer
• Bill Saxton (MCD) Organelle Transport and Neurodegeneration
• Bill Scott (Chem) Understanding the Structure-based Mechanisms of Ribozyme-based Theraputic Agents
• Nik Sgourakis (Chem) Modelling the Structures of Protein Complexes from Sparse Experimental Data
• Michael Stone (Chem) Assembly, Structure, and Regulation of the Telomerase Ribonucleoprotein
• Hongyun Wang (AMS) The ATP Synthase Modeling Project
• Alan Zahler (MCD) Regulation of Pre-mRNA Splicing and Post-Transcriptional Regulation by Micro RNAs
• Jin Zhang (Chem) The Application of Molecular and Nanomaterial Systems to the Detection and Treatment of Cancer


Prof Mark AkesonControl and Analysis of DNA and RNA Using Nanoscale Pores

Mark Akeson, Biomolecular Engineering

Mark Akeson's research is focused on the use of nanopore detectors - instruments built around a tiny pore in a membrane or thin, solid-state wafer. These pores are just big enough to allow a single strand of DNA to pass through. Akeson and his collegues use the detectors to understand the dynamics and structure of DNA duplex ends, including those of retrotransposons and HIV. Akeson also investigates the coupling of processive DNA-modifying enzymes to nanopores, both protein and solid-state. Together with UCSC Professors William Dunbar and David Deamer, he has demonstrated enzymatic control of single DNA in nanopores with sequence specificity and real-time feedback control. [More]

Akeson Publications
Mark Akeson's Email


Prof Hinrich BoegerPromoter Chromatin Dynamics and Gene Expression

Hinrich Boeger, MCD Biology

Research in Hinrich Boeger’s laboratory is concerned with the structure and dynamics of chromatin at gene regulatory elements. The eukaryotic cell packages its nuclear DNA by spooling the DNA in regular intervals about a core of specific proteins, forming a jointed chain of DNA spools (‘nucleosomes’). This chain, or ‘chromatin fiber’, folds up into unknown structures of higher order. How does DNA spooling affect both gene expression and regulation, which both require access to the DNA? This question is pursued by molecular biological and biophysical methods, including electron and fluorescence microscopy and yeast genetics. These experimental approaches are combined with mathematical modeling of promoter chromatin dynamics and function. The aim is the development of a formal framework that allows for a quantitative understanding of eukaryotic gene expression and regulation. [More]

Boeger Publications
Prof. Boeger's Email

Prof BowmanMembrane Function and Calcium Regulation

Barry Bowman, Dept. of MCD Biology

One third of the genes in all organisms encode membrane proteins, most of which transport molecules from one compartment to another. We use Neurospora crassa as our model organism. The complete genome has been sequenced for this filamentous fungus. It has 10,000 genes, twice the number in yeast, and a complete collection of knockout mutants is being generated. [More]

Bowman Publications
Barry Bowman's E-Mail

Prof Phil CrewsMarine Natural Products as Potent Agents Against Human Disease

Phil Crews, Dept. of Chemistry and Biochemistry

A primary goal of Phillip Crews' marine natural products research is to understand the chemistry of tropical marine sponges. Using bioassay-guided isolation assists us in the discovery of natural products potent against human diseases, such as cancer or viruses. Their search for novel active compounds incorporates elements of structure elucidation, but there are other dimensions to this research, including questions in the areas of chemical ecology, marine natural products biosynthesis, and the relationship between secondary metabolite chemistry and taxonomy... [More]

Crews' Publications Phil Crews' E-Mail

Prof DeamerNanopore Methods of DNA Analysis

David Deamer, Biomolecular Engineering

Professor David Deamer and his collaborators have developed a nanopore device that captures single nucleic acid molecules and analyzes their structure, dynamic motion and base sequences. [More]

Deamer's Publications Dave Deamer's E-Mail

 


Prof DuBoisStructure, Function, and Engineering of Virus Proteins

Rebecca DuBois, Biomolecular Engineering

Professor DuBois is a structural biologist studying viral surface and replication proteins. She uses her discoveries to design novel vaccines, to develop nanoscale drug delivery vehicles, and to develop antiviral therapeutics. [More]

DuBois Publications Rebecca Dubois' E-Mail

 


Prof Einarsdottir

Structure, Mechanisms, and Dynamics of Respiratory Heme-Copper Oxidases

Ólöf Einarsdóttir, Chemistry and Biochemistry

Ólöf Einarsdóttir's Laboratory is interested in fundamental properties of energy transfer in living organisms. Their work focuses on the respiratory chain that provides energy for the cell. Einarsdóttir's principle focus is on the structure, mechanisms, and dynamics of heme-copper oxidases, which play a key role in respiration. This research will have significant implications for human health, because of 1) increased virulence of certain pathogens conferred by the presence of certain terminal bacterial oxidases, 2) the NO inhibition of cytochrome oxidase and its potential physiological regulation of cellular respiration, and 3) the fundamental role of the interaction of O2, NO and CO with cellular functions related to aerobic metabolism and signaling. [More]

Einarsdóttir's Publications Einarsdóttir' E-Mail

Prof HolmanLipoxygenase Inhibitors as Potential Anti-Inflammatory Drugs

Ted Holman, Dept. of Chemistry & Biochemistry

Lipoxygenases are enzymes implicated in a broad range of inflammatory diseases, such as diabetes, heart disease, and stroke, to name a few. Ted Holman's laboratory examines the enzymatic mechanism and biological function of lipoxygenase in the hopes of understanding how the enzyme functions and developing novel inhibitors. In collaboration with medical school collaborators, his laboratory has identified potent lipoxygenase inhibitors and are currently characterizing their structure/function reactivity. The results of this work will shed light on their potential as anti-inflammatory agents. [More]

Holman's Publications Ted Holman's E-Mail

Prof Melissa JuricaStructure and Functional Analysis of Spliceosomes

Melissa Jurica, MCD Biology

The Jurica lab investigates the cellular machinery responsible for editing the information contained in the RNA transcripts of nearly all of human genes. This machinery, called the spliceosome, uses a molecular “splicing” reaction to cut out intron sequences that interrupt gene transcripts and joins exon sequences to make messenger RNAs that correctly encode for proteins. Splicing is a key step of gene expression and its misregulation is linked to many genetic diseases, including cancers and neurodegenerative disease. Juric'a goal is to determine how the spliceosome is assembled and how it catalyzes the splicing reaction. The lab's reasearch will provide a basic foundation for understanding what goes wrong with splicing in disease situations. [More]

Melissa Jurica's Publications Melissa Jurica's E-Mail

Prof KelloggControl of Cell Growth and Size

Doug Kellogg, Dept. of MCD Biology

Cells show extraordinary diversity in size and shape.  The mechanisms by which cells control their growth and size are poorly understood and represent a fundamental unsolved problem in cell biology.  The goal of the Kellogg laboratory's work is to elucidate these mechanisms. Their approach is to use biochemistry, genetics, and mathematical modeling to understand signaling networks that are required for control of cell size and cell growth. [More]
Kellogg's Publications Doug Kellogg's E-Mail

Prof KligerDynamics of Biomedical Molecules in Vision, Allostery, and Folding

David Kliger, Chemistry & Biochemistry

The Kliger lab uses time-resolved spectroscopy to study protein reactions. Proteins are central to health, making study of their structure and function critical. While traditional biochemical methods provide insight about the later steps in function, modern optical methods (particularly pulsed lasers and polarized light) reveal previously unknown steps occurring on short time scales, which are important in biomedical processes. Such information can lead to new insights into fundamental biological processes, as well as guides to the development of new and more effective drug therapies. [More]

Kliger Publications Dave Kliger's Email

Prof Joel KubbyApplications of Adaptive Optics for Biological Microscopy

Joel Kubby, Dept. of Electrical Engineering

Professor Joel Kubby is collaborating with engineers, physicists and biologists to utilize Adaptive Optics for the improvement of deep tissue imaging of living cells. Current biological microscopy is incapable of obtaining high quality live imaging in samples greater than 30 microns beneath the plasma membrane, where many critical cellular processes occur. Much of the degradation in image quality is the result of local differences in the refractive index, both within the sample and between the sample and the immersion lens. Adaptive optics was first used to correct for image aberrations in astronomical imaging. Kubby and his collaborators have shown that the same principles that improved resolution in telescopes can be adapted to improve wide-field, confocal, two-photon, super-resolution and spinning disk microscopy systems that are crucial for biological research. [More]
Kubby Publications Joel Kubby's Email

Prof Scott LokeyA Small Molecule Approach for Studying Signaling Pathways Related to Cell Motility and Cancer

Scott Lokey, Chemistry and Biochemistry

The laboratory of Scott Lokey uses a small molecule approach, called chemical genetics, to study signaling pathways related to cell cycle checkpoints and the actin cytoskeleton. In one study, Lokey and his co-workers are developing screens of natural compounds that can be used to examine how cells detect their own DNA damage. Studies such as these might lead to development of a new class of chemotherapeutic agents. [More]

Lokey Publications Lokey's E-Mail

xxxDelivery of Small Messenger Molecules to Biological Targets

Pradip Mascharak, Chemistry and Biochemistry

Dr. Pradip Mascharak’s bioinorganic chemistry laboratory conducts basic and applied research regarding metal-based, nitric oxide (NO) and carbon monoxide (CO) carriers that release NO (or CO) when activated by light. In cancer cells, NO induces apoptosis (programmed cell death), which is the primary cellular mechanism of tumor clearing in chemotherapeutic treatments. Unlike conventional chemotherapy where the drug is distributed systemically, Mascharak’s synthetic “NO donors” allow unique control over where, when, and how much NO is released. Various chemical principles guide the design of such nitrosyls (NO carriers) that deliver NO to biological targets under specific conditions. Results of parallel theoretical studies are also utilized to elucidate the electronic origin of the NO photolability. This “photodynamic” approach has intriguing implications for the development of drugs in treating skin and other cancers. Recently the group has turned their focus on CO, another surprising addition to the list of small signaling molecule in biology. Low doses of CO has been shown to provide cytoprotective action to oxidatively damaged tissues (such as during stroke and ischemia). Mascharak's group has initiated syntheses of designed metal-CO complexes (based on Smart Design principles) that readily deliver CO to damaged tissues and neoplastic sites. Attempts are also being made to attach these NO/CO donors on inert matrices and employ the composites in catheters, powders, or patches for delivery of these two gaseous "drugs" in hospital settings. [More]

Mascharak Publications Pradip Mascharak's Email

Prof MillhauserRemarkable Protein Structures ..... and Where They Go Wrong

Glenn Millhauser, Department of Chemistry

In modern biochemistry, structural determination is essential for understanding the function of biomolecules. Scientists in Glenn Millhauser's laboratory use peptide synthesis, nuclear magnetic resonance spectroscopy (NMR), and electron paramagnetic spin resonance spectroscopy (EPR) to examine the structure and analyze the function of proteins that have been implicated in several debilitating diseases. This includes the prion protein, which is responsible for mad cow disease and the related human affliction, Creutzfeldt-Jakob disease. They have also examined a novel signaling molecule, called AGRP, which is involved in energy balance and metabolic pathologies, such as diabetes and obesity. [More]

Millhauser Publications Glenn Millhauser's E-Mail

Prof Karen OttemannHow Bacterial Pathogens Sense and Respond to Host Environments

Karen Ottemann, Dept. of Microbiology and Environmental Toxicology

Professor Karen Ottemann's laboratory investigates how bacteria translate chemical and physical cues in their host environment into pathogenic outcomes. Mistakes in sensation and subsequent gene expression by bacteria may result in their elimination by the host immune response or peristaltic flow. Elucidation of such processes will hopefully lead to identification of anti-bacterial drug targets. Ottemann is particularly interested in the role of outer membrane proteins and chemotaxis associated with the bacterium Helicobacter pylori. This pathogen infects some 3 billion humans and can lead to serious disease, including ulcers and cancer. [More]

Ottemann Publications Karen Ottemann's Email

Prof Rubin Exploring the Molecular Basis for Circadian Timekeeping in Mammals

Carrie Partch , Chemistry and Biochemistry

Mammalian physiology is synchronized into 24-hour rhythms that coincide with the solar day by an intrinsic molecular clock. As a global regulator of homeostasis, disruption of the circadian clock has profound consequences on human health, leading to depression, metabolic syndromes, cancer, and premature aging. The Partch lab studies how the 24-hour periodicity of this molecular clock is generated and how it integrates with the cell cycle to limit proliferation using cell biology, biochemistry and biophysical techniques. They are also interested in chemical biology approaches to modulate clock timing with structurally informed in vitro and cell-based screening platforms. [More]

Partch Publications Carrie Partch's E-Mail


Prof Nader PourmandSingle Cell Analysis and Manipulation, Biosensor, Nanotechnology, DNA Sequencing

Nader Pourmand, Dept. of Biomolucular Engineering

The Pourmand lab develops new tools and technologies that integrate biology, electronics, and nanofabrication for the detection and study of genes and proteins. These tools are specifically designed to increase the speed and lower the cost of sample analysis. The lab directs particular attention to the development of medically relevant technology, such as instruments for single cell analysis. Pourmand is also Director of Genome Technology Center. [More]

Pourmand Publications Pourmand's Email

Prof. Jevgenij A. RaskatovDisease-Oriented Chemical Biology

Jevgenij A. Raskatov, Dept. of Chemistry and Biochemistry

Raskatov draws inspiration from aging-related medicinally challenging questions, which are becoming increasingly pressing as life expectancy continues to rise (the cancer/inflammation interface is of specific interest). Raskatov's lab identifies biomolecular signaling nodes that are sufficiently well-understood at the molecular level, so that a biology problem can be translated into a chemistry problem. As chemists, their goal is to synthesize molecules and study their properties by means of NMR spectroscopy (1), crystallography (2) and DFT computation (3). Molecular scaffolds that show initial promise are tested in relevant biological systems both in cell culture (4) and in vivo (5). [More]

Raskatov Publications Jevgenij Raskatov's Email

Prof RubinMolecular Mechanisms of Cell Cycle Regulation and Cancer

Seth Rubin, Chemistry and Biochemistry

The Rubin laboratory uses a variety of structural and biochemical techniques to investigate the molecular mechanisms that control the eukaryotic cell cycle. The aim is to elucidate detailed molecular pictures of protein-protein interactions and how these interactions are regulated by structural and chemical modifications. Improper regulation of these protein interaction networks is commonly associated with aberrant cell proliferation and cancer. [More]

Rubin Publications Seth Rubin's E-Mail


Prof Bill SaxtonOrganelle Transport and Neurodegeneration

Bill Saxton, Dept. MCD Biology

The Saxton lab studies mechanisms that drive intracellular transport and cytoplasmic organization, using Drosophila as a model organism. To generate and maintain proper cytoplasmic order and thus their complex functions, cells use microtubules and force-generating motor proteins to transport RNAs, proteins, mitochondria and other organelles to appropriate locations. Neurons are especially dependent on such microtubule-based cytoplasmic transport, because their signaling functions rely on extraordinarily long cytoplasmic extensions (axons and dendrites) that require import of many components from their cell bodies ... [More]

Saxton Publications Bill Saxton's Email

Prof Scott
RNA Catalysis

William Scott, Dept. of Chemistry and Biochemistry

Ribozmes are RNA-based enzymes whose comparatively recent discovery came as major surprize to the scientific community, as it has always been assumed that only proteins could be enzymes. Researchers in the Scott laboratory are trying to understand how ribozymes work, using X-ray crystallography and other biochemical and biophysical techniques. The potential use of ribozymes as therapeutic agents that target RNA viruses (such as HIV) and pathological mRNAs (such as oncogene transcripts) is well-documented. Although the primary motive for our research is to answer questions of a fundamental scientific nature, it is hoped that the results of these studies will provide practical information to the scientific and medical communities to enable more potent and effective ribozyme-based pharmaceuticals to be developed by others. [More]

Scott Publications Bill Scott's E-Mail

Prof Nik SgourakisModelling the Structures of Protein Complexes from Sparse Experimental Data

Nik Sgourakis, Dept. of Chemistry and Biochemistry

Research in the Sgourakis lab focuses on elucidating the structures of important protein complexes involved in Immune recognition of viruses, bacterial secretion and neurodegeneration. Determining the structural basis of protein-protein interactions and self-assembly will help clarify fundamental biological mechanisms and facilitate the design of novel therapeutics. To achieve this, structure-based modelling at sufficient resolution is required. The Sgourakis lab is developing and implementing new tools based on Nuclear Magnetic Resonance spectroscopy and complementary sources of experimental data alongside advanced computational sampling methods. The integration of a range of experimental and computational approaches enables structural studies of proteins and their complexes at high resolution. [More]
Sgourakis Publications Nik Sgourakis' Email

Prof Michael StoneAssembly, Structure, and Regulation of the Telomerase Ribonucleoprotein

Michael Stone, Dept. of Chemistry and Biochemistry

The Stone Research Group combines the use of biochemical and structural methods with newly emerging single-molecule techniques to probe the dynamics of protein-nucleic acid interactions and the molecular mechanisms of biological motors.  Our current area of focus is the structure and function of the telomerase ribonucleoprotein, an RNA-dependent DNA polymerase that maintains genomic stability by synthesizing repetitive DNA sequences at chromosome termini.  These short DNA repeats provide the foundation for specialized chromatin structures, called telomeres, which prevent deleterious chromosome fusion events by differentiating chromosome ends from sites of DNA damage.  It has been shown that telomere length typically decreases with every round of cell division, leading to the so-called ‘molecular clock’ hypothesis, wherein telomere length serves as a signal to control cellular lifespan. This notion is consistent with the finding that active telomere DNA synthesis is normally restricted to rapidly dividing cell types such as stem cells and the majority of human cancers. Our research seeks to elucidate physical mechanisms governing telomere length regulation, and in turn establish a conceptual framework within which to develop novel diagnostic and therapeutic strategies for human disease. [More]

Stone Publications Michael Stone's Email


Prof Hongyun WangThe ATP Synthase Modeling Project

Hongyun Wang, Dept. of Applied Mathematics and Statistics

Hongyun Wang uses both biophysics and molecular modeling techniques to examine mechanisms that convert chemical energy of ATP into mechanical work in biological systems. [More]

Hongyun Wang's Publications Hongyun Wang's Email

Prof Al ZahlerRegulation of Pre-mRNA Splicing and Post-Transcriptional Regulation by Micro RNAs

Alan Zahler, MCD Biology

The human genome carries the blueprint for the creation of proteins, the molecular machines that carry out most of the work in the body. However, the diversity of the pool of available proteins is greatly enhanced by alterative splicing of our genes. The Zahler laboratory examines the nematode Caenorhabditis elegans in order to understand the regulatory mechanisms of this alternative splicing. Small RNAs such as miRNAs, piRNAs, and siRNAs play important roles in gene regulation at many different levels. Zahler's group is studying small RNA biogenesis and the role of small RNAs in the regulation of genomic rearrangements in ciliated protozoans. [More]

Zahler Publications Alan Zahler's E-Mail

Prof Jin ZhangThe Application of Molecular and Nanomaterial Systems to the Detection and Treatment of Cancer

Jin Zhang , Dept. of Chemistry and Biochemistry

The Zhang research group is interested in the application of molecular and nanomaterial systems in conjunction with optical spectroscopy and related techniques for biomedical detection and treatment, with emphasis on cancer therapies and cancer biomarker detection.  Specific projects include: 1) investigation of mechanisms of photodynamic therapy and catalytic therapy based on porphyrins, phthalocyanines, and related compounds; 2) detection of small molecule, protein, and DNA cancer biomarkers using fluorescence based on quantum dots (QDs) and surface-enhanced Raman scattering (SERS) based on metal nanostrutcures; and 3) photothermal imaging and therapy of cancer using unique metal nanostructures.  This research involves systematic study of the structural, optical, and photophysical as well as photochemical properties of the materials using a combination of microscopy, x-ray, spectroscopy, and electrochemistry techniques. [More]
Zhang Publications Jin Zhang's Email
 

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