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STRUCTURAL BIOLOGY
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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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 Structure
and Functional Analysis of Spliceosomes
Melissa Jurica, MCD Biology
The Jurica lab uses the tools of structural biology
and biochemistry to investigate the cellular machinery responsible
for editing the information contained in the RNA transcripts of nearly
all of human genes. This machinery, called the spliceosome, splices
out intron sequences that interrupt gene transcripts and joins exon
sequences to make messenger RNAs that correctly encode for proteins.
The goal of Jurica's research is to understand how the spliceosome
is assembled and how it catalyzes the splicing reaction, but this is
..... [ More] |
 Protein
Structure Prediction and Design
Kevin Karplus, Dept. of Biomolecular Engineering
Kevin Karplus' research group develops tools
and techniques for protein structure prediction and protein design.
He collaborates with Richard Hughey's group on the development of
the SAM tool suite for profile hidden Markov models, particularly
on developing protocols for using the tools for high-accuracy detection
of remote relationships between proteins. Karplus' group has used
these tools themselves to earn an international reputation for accurate
prediction of protein structure: secondary structure, tertiary structure,
and contact prediction. In the biannual Critical Assessment of Structure
Prediction "contests", his group has presented papers (the "prize" for
the contest) in CASP2 through CASP7. The group also collaborates
extensively with UCSC wet-lab biologists in predicting structure
and function for proteins of interest to them, and is starting work
on designing novel proteins. [More]
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 Remarkable
Protein Structures ..... and Where They Go Wrong
Glenn Millhauser, Department of Chemistry
In the laboratory of Glenn Millhauser, investigators
use peptide synthesis and magnetic resonance to investigate the structure and
function of biomolecules. These studies include analysis of proteins involved
in devastating metabolic and neurological diseases. [More]
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Structure and Function of the Ribosome
Harry Noller, MCD Biology
Ribosomes are RNA-based molecular
machines that are responsible for synthesis of proteins. Researchers
in the Noller laboratory were the first to solve the complete structure
of a ribosome using X-ray crystallography. Besides the importance of
protein synthesis to understanding the molecular basis of cellular
function, research on ribosomes promises to improve the design of new
antibiotics. Many of today's most effective anti-microbial drugs work
by targeting bacterial ribosomes. As pathogenic bacteria continue to
develop resistance to commonly used antibiotics, clarification of the
structure and molecular mechanisms of bacterial ribosomes will be critical
for the design of new drugs that will keep pace with rapidly evolving
bacteria. [ More] |
 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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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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