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CHROMOSOME BIOLOGY
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 Chromosome
Structure and Function during Meiosis
Needhi Bhalla, Dept. of MCD
Biology
The Bhalla lab is interested
in the mechanisms that ensure that chromosomes segregate correctly during cell
division, particularly in meiosis. During this specialized cell division, diploid
cells give rise to haploid gametes, such as sperm and eggs, so that diploidy
is restored by fertilization. Defects in meiosis can generate gametes and, therefore,
embryos with the incorrect number of chromsomes. These aberrations in chromosome
number, also referred to as aneuploidy, typically produce inviable embryos.
It is estimated that 30% of human miscarriages are due to aneuploidy. In some
cases, the presence of an extra copy of a chromosome can be tolerated by a human
embryo but results in serious developmental disorders, such as Down and Klinefelters
syndrome. [More]
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 The
Dynamics and Function of Chromatin Structure in Gene Regulation
Hinrich Boeger, MCD Biology
Eukaryotic organisms (plants, fungi and animals belong to
this group) package their genomes by spooling their DNA around basic protein
cores. The spools are called nucleosomes, and are one of the critical features
that distinguish eukaryotic cells from their bacterial relatives. Similar to
beads on a string, nucleosomes form in regular intervals on the DNA. Such strings
of nucleosomes (chromatin) fold up to higher levels of compaction. Thus, nucleosomes
serve as general inhibitors of gene expression by limiting access of the transcription
machinery and its regulatory proteins to the DNA. Consequently, chromatin structures
must locally unfold to allow genes to be expressed. Research in Hinrich Boeger's
lab focuses on the unfolding of chromatin structures in the context of gene
regulatory events. [More]
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 How
Chromatin Influences Transcription
Grant Hartzog, Dept. of MCD Biology
Grant Hartzog's laboratory investigates the roles
of proteins that regulate the rate of transcription elongation - i.e. how quickly
RNA polymerases travel along and transcribe genes into RNA. Many normal cellular
genes are known to be regulated at the level of elongation, and the HIV virus
specifically co-opts normal transcription elongation factors to regulate its
own replication. Thus, understanding how transcription elongation is controlled
is important for an understanding of both normal and abnormal gene expression.
[More]
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 Genome
Bioinformatics: Comparative Sequence Analysis of Mammalian Genomes
David Haussler, Dept. of Biomolecular Engineering
Dr. Haussler's research lies at the interface
of mathematics, computer science, and molecular biology. He has focused
on computational analysis and classification of DNA, RNA, and protein
sequences. As a collaborator on the public Human Genome Project,
his team posted the first publicly available computational assembly
of the human genome sequence on the Internet, and it now maintains
UCSC's Genome Browser, which is used extensively in biomedical research.
[More]
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 Transcriptional
Silencing and Insulators
Rohinton Kamakaka, Dept. of MCD Biology
Rohinton Kamakaka is interested in how physical and
functional organization of chromatin influences gene regulation. His lab focuses
on the mechanism by which the genome is partitioned into structural and functional
units. Using molecular and genetic analysis, coupled with biochemical experiments,
the group is presently investigating the architecture of silenced chromatin
domains, as well as the mechanism by which chromatin domains are delimited.
[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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 Structure,
Function, and Assembly 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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 Regulation
of Germ Cell Development in C. elegans
Professor Susan Strome, MCD Biology
Germ cells (the cells that give rise
to eggs and sperm) have special properties. Their immortality allows them
to be perpetuated from generation to generation, and their totipotency allows
them to generate all of the diverse cell types of the body in each generation. The
Strome lab investigates the molecular mechanisms used by germ cells to establish
and maintain their identity, immortality, and totipotency. They study
germ cells in the model organism C. elegans using
a wide variety of approaches, including forward genetics, RNAi, imaging, molecular
biology, biochemistry, and whole genome microarray-based technologies. Their
current focus areas are control of gene expression in germ cells by regulation
of chromatin, and control of RNA metabolism by germline-specific cytoplasmic "P
granules". [More]
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 Cell
Cycle, Cytoskeleton and Pathogenesis
Bill Sullivan, Dept. of MCD Biology
The Sullivan lab uses the Drosophila embryo
as a model system to investigate the mechanisms that drive furrow
invagination during cytokinesis. Through a combination of cellular
and molecular genetic approaches, the Sullivan group has showed that
furrow formation requires coordinated cell cycle regulated and endocytic-based
vesicle recruitment. These studies have also identified a new role
for cell cycle checkpoints in coordinating the nuclear cycle with
cytokinesis. More recently, the lab has applied these approaches
toward understanding the mechanisms by which the widespread intracellular
insect pathogen, Wolbachia, influences host nuclear and
cytoplasmic cell cycles. [More]
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 Regulation
of Chromatin Structure and Gene Expression
John Tamkun, Dept. of MCD Biology
The Tamkun lab investigates regulation of chromatin's
high order structure and its role in gene expression. Composed of DNA and proteins,
chromatin's ability to fold enables the eukaryotic genome to be packaged into
an extremely small space inside the nucleus of the cell. Proper transcription
and replication of the genome also depend upon precise regulation of these dynamic
structures, with defects in these processes believed to underly many human diseases.
[More]
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