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BIOCHEMISTRY AND BIOPHYSICS
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Control and Analysis of DNA and RNA Using Nanoscale Pores
Mark Akeson, Dept. of 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]
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The Dynamics and Function of Chromatin Structure
Hinrich Boeger, Dept. of MCD Biology
Eukaryotic organisms must package an enormous amount of genetic information in their chromosomes. DNA and proteins form a complex called chromatin, which enables this information to be compacted into a very small space within the nucleus. However, these chromatin structures must also be periodically unfolded in order to make genes accessible to regulatory factors and the molecular machinery that transcribes their information to make functional proteins for the cell. Hinrich Boeger's lab studies the unfolding of chromatin structures in the context of gene regulatory events. [More]
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Membrane 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]
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Marine
Natural Products as Anti-Cancer Compounds
Phil Crews, Dept. of Chemistry and Biochemistry
The Crews laboratory investigates
the chemical structure and biological activity of chemical compounds that are
derived from marine organisms. Among its many research projects, the laboratory
collaborates with scientists at other research institutions and pharmaceutical
industries to explore the identification and development of naturally occuring
compunds in the fight against cancer. [More]
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Nanopore
Methods of DNA Analysis
David Deamer, Biomolecular Engineering
Professor David Deamer and his collaborators
investigate physical properties of single DNA molecules. Together, they developed
a biomolecular nanopore detector that rapidly discriminates between nearly identical
strands of DNA. [More]
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Linking Energy Metabolism and Oxygen Utilization
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 an enzyme called cytochrome
oxidase. Chemical, structural, and functional analyses of this enzyme promise
to provide important insight into its role in certain diseases. [More]
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Lipoxygenase
Inhibitors as Potential Anti-Cancer Drugs
Ted Holman, Dept. of Chemistry & Biochemistry
Lipoxygenases are enzymes implicated in a broad range
of human cancers, as well as cardiac and inflammatory diseases. Ted Holman's
laboratory examines the enzymatic mechanism and biological function of lipoxygenase
in the hopes of developing novel inhibitors. In collaboration with UCSC Professor
Phil Crews, 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-cancer agents. [More]
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Dynamics 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 a short time scale, which are important in biomedical processes.
Such information can lead to the development of new and more effective drug
therapies. [More]
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A
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]
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Light-Activated
Nitric Oxide Carriers: A New Path in Cancer Treatment
Pradip Mascharak, Chemistry and Biochemistry
Dr. Pradip Mascharak’s bioinorganic
chemistry laboratory conducts basic and applied research regarding metal-based,
nitric oxide (NO) carriers that release NO 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. This “photodynamic” approach has intriguing
implications for the development of drugs in treating skin and other cancers.
[More]
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Remarkable
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]
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Molecular
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]
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How
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 adaptive responses. 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 chemoreceptors 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. Ottemann and her colleagues have discovered
two of the first chemoreceptors known to aid in the process of bacterial colonization.
[More]
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Tools
for Studying Genes and Proteins
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 pathogen detection. Pourmand is also spearheading UCSC's
effort to establish a new high-throughput, high-quality sequencing facility.
[More]
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Organelle
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]
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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]
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Assembly,
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]
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The
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]
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Regulation
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. [More]
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The
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]
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