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AGING
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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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Remarkable
Protein Structures... and Where They Go Wrong in Disease
Glenn Millhauser, Dept. of Chemistry and Biochemistry
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] |
Origin
and Regulation of Mammalian Stem Cells
Amy Ralston, Dept. MCD Biology
Understanding the origins
of stem cells in the embryo is essential for understanding how to guide
formation of stem cell-derived tissues. Several stem cell-producing
tissues exist in the early mouse embryo, which provides an ideal system
for exploring mechanisms that guide stem cell development. In addition,
stem cells can be artificially created by genetic reprogramming mature
cells. We are interested in understanding how natural and reprogrammed
stem cells compare. We use a variety of techniques, including mouse
transgenics, bioinformatics, molecular biology, and confocal microscopy
to examine the establishment and use of stem cells during normal development.
From these studies, we hope to understand the molecular basis of cell
fate and plasticity, as they relate to normal development and regenerative
medicine. [ More]
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Post
Transcriptional Control of Gene Expression
Jeremy Sanford , Dept.
of MCD Biology
Accumulation of somatic mutations
during our life history contributes to the stochastic nature of aging
and plays a key role in the onset of disease. The focus of this project
is to understand how mutations induce disease phenotypes, a question
directly relevant to many aspects of aging research. Here we investigate
the hypothesis that disease-causative point mutations induce aberrant
processing of messenger RNA by disrupting the specificity of protein-RNA
interactions. Our first step towards elucidating the impact of disease-causing
mutations will be to map sites of RNA-protein interactions occurring
in the context of living cells. These comprehensive maps will be leveraged
to identify disease-causing mutations with the potential to abolish
or create protein-binding sites within RNA transcripts. Our computational
predictions of toxic RNA elements will be validated in the laboratory
using patient-derived cell lines to assay RNA processing of the endogenous
disease-gene. Our work in this area promises to improve our understanding
of the basic mechanisms governing gene expression and will directly
translate to improved diagnosis and treatment of aging related diseases. [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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Organismal
Responses and Therapeutic Treatment of Toxins
Don Smith, Microbiology and Environmental Toxicology
It is becoming clear that exposures
to environmental toxins, such as lead, mercury, and arsenic can cause or contribute
to the development of diseases in humans. For example, some neurobehavioral
and neurodegenerative disorders, such as learning deficits and Parkinsonism
have been linked to elevated lead and manganese exposures in children and manganese
exposures in adults, respectively. The Smith lab explores basic mechanisms underlying
how toxic metal exposures contributes to cellular effects and disease. [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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Glia-neuron
Interaction and Structural Plasticity of the Synapse
Yi Zuo, Dept. of MCD Biology
Neurons communicate with each
other at a specialized structure called the synapse. The Zuo lab focuses on
how the interactions of two types of cells - glia and neurons - affect synapse
formation and plasticity. Zuo's studies are providing insight into the involvement
of glia in learning and memory. Furthermore, because glial malfunctions are
characteristic of many neurodegenerative diseases, her lab's results may also
point us in the direction of potential treatments for neurological diseases.( [More]
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