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BIOCHEMISTRY,
MOLECULAR BIOLOGY & CHEMICAL BIOLOGY
Biology is a broad field of study, and its breadth
is reflected in the research interests of the
faculty members who seek to define biological
processes in molecular terms. Individual research
topics include the role in vivo of an enzyme
with a catalytic RNA subunit (Altman);
engineering new RNA and DNA enzymes by rational
design and in vitro evolution (Breaker);
exploration and control of signal transduction
pathways using chemical probes (Crews);
the evolution of metabolic pathways (Ornston),
and signal transduction in plants.
Molecular technology from DNA cloning to targeted
mutagenesis is being applied and developed in
order to elucidate the molecular mechanisms underlying
many biological processes. Insight into these
processes can be greater when it is gained in
the spectrum of diverse experimental approaches
that our division employs. Our studies will eventually
bring together molecular biology, evolutionary
biology, cell and developmental biology, and genetics.
Our studies can directly benefit human health
and agricultural efficiency.
Faculty having a Primary Affiliation with this
Section
Sidney Altman : post-transcriptional RNA processing
as a means of gene regulation
Ronald
Breaker : enzymatic DNA and in vitro evolution
Craig Crews
: biochemical and molecular analyses of
natural products
Richard
Flavell :T cell tolerance activation and its
consequences in autoimmunity are studied by the
application of targeting and transgenic technology.
Mark
Hochstrasser : the life and death of proteins:
regulation by ubiquitin and the proteasome.
Nicholas
Ornston :evolutionary relationships among
a set of genes which have coevolved within a single
cell line.
Alanna
Schepartz : Chemical and molecular basis of
transcription: design of functional miniature
proteins and assemblies.
Additional
Faculty with Interests in Molecular Biology
Stephen
Dellaporta : molecular biology and genetic
utility of transposons in plants.
S.P.
Dinesh-Kumar : molecular basis of host-pathogen
interactions in plants.
Thierry Emonet: Relating network architecture to biological function using computational modeling and experiments.
Christine
Jacobs-Wagner : use of Caulobacter crescentus
to study genetic circuitry which controls cell
cycle.
Thomas
Pollard : the molecular basis of cellular
motility and cytokinesis.
Joel
Rosenbaum : assembly of cell organelles using
the flagella of Chlamydomonas as a model.
William
Segraves : molecular and genetic
analysis of the insect steroid molting hormone
ecdysone in Drosophila.
Michael
Snyder : molecular, cellular and genetic analysis
of cell structure and division in eukaryotes.
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CELLULAR & DEVELOPMENTAL BIOLOGY
The
research interests of the faculty in the area
of cell and developmental biology range from studies
on nucleotide sequences in RNA and DNA through
investigations of subcellular organelles, such
as microtubules and chromosomes, to analyses of
movement in single cells, and embryogeny in higher
plants and animals.
Despite
the diversity of research topics and an equal
diversity of experimental approaches, certain
general aims are evident. These include the understanding
of how macromolecules are organized into the subcellular
components of living cells, how the cells themselves
become different during development, and how the
cellular and developmental processes are controlled.
Faculty
having a Primary Affiliation with this Section
Kim
Bottomly : regulation and function of CD4
T lymphocytes.
Iain
Dawson : regulation of cell cycle in Drosophila
melanogaster
Xing-Wang
Deng : molecular mechanisms involved in light-triggered
regulation of growth and development in higher
plants.
Martín
García-Castro : the origin of neural
crest cells.
Mary
Helen Goldsmith : role of auxin as a growth
and development regulator in plants.
Scott
Holley : Genetic analysis of vertebrate
segmentation in the zebrafish, Danio rerio.
Vivian
Irish : mechanisms that govern pattern formation
during plant development.
Christine
Jacobs-Wagner : use of Caulobacter crescentus
to study genetic circuitry which controls cell
cycle.
Michael
Kashgarian : Na, KATPase expression: epithelial
cell polarity; heat shock protein functions.
Mark
Mooseker : molecular underpinnings of cytoskeletal
structure, motility and assembly.
Jon
Morrow : understanding the structure and function
of the spectrin-ankyrin-actin cytoskeleton.
Kenneth
Nelson : host-parasite interactions in human
filarial nematode diseases.
Timothy
Nelson : development of leaves.
Thomas
Pollard : the molecular basis of cellular
motility and cytokinesis.
Joel
Rosenbaum : assembly of cell organelles using
the flagella of Chlamydomonas as a model.
Frank
Ruddle : genetic and cell biological analyses
of development in the mouse.
Michael
Snyder : molecular, cellular
and genetic analysis of cell structure and division
in eukaryotes.
Joseph
Wolenski : molecular analysis of myosin mechanochemistry.
Additional
Faculty with Interests in Cell and Developmental
Biology
John Carlson : molecular and genetic analysis
of olfactory system in Drosophila.
Craig
Crews : biochemical and molecular analyses
of natural products.
Thierry Emonet: Relating network architecture to biological function using computational modeling and experiments.
Paul
Forscher : molecular dynamics of guided axon
growth.
Mark
Hochstrasser : the life and death of proteins:
regulation by ubiquitin and the proteasome.
Douglas
Kankel : genetic and molecular analysis of
visual system development in Drosophila.
Haig
Keshishian : analysis of neuromuscular development
in Drosophila.
Shirleen
Roeder : genetic and molecular analysis of
meiosis in yeast.
William
Segraves : molecular and genetic analysis
of the insect steroid molting hormone ecdysone
in Drosophila.
Frank
Slack : microRNAs
in development and disease.
Elke Stein
: the molecular mechanism that underlies neuronal
growth cone guidance.
David
Wells : examination of the process of experience
dependent modification (or plasticity) of synapses
at the cellular and molecular levels.
Robert
Wyman : analysis of genes which control the
specificity of neuronal connectivity in Drosophila.
Weimin
Zhong : regulation of neural stem cells and
development of the mammalian neocortex.
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GENETICS
Research
in this fundamental area of biology spans a spectrum
of biological organization from the molecular
level to the organismal level. The underlying
focus of interest is the genetic material: its
structure, function, and regulation. A large variety
of organisms is being studied using many experimental
techniques and approaches. The Department has
laboratories active in molecular and biochemical
genetics, developmental genetics, molecular and
classical cytogenetics, somatic cell genetics,
and behavior genetics.
Faculty
having a Primary Affiliation with this Section
John Carlson : molecular and genetic analysis
of olfactory system in Drosophila.
Stephen
Dellaporta : molecular biology and genetic
utility of transposons in plants.
Scott
Holley : Genetic analysis of vertebrate segmentation
in the zebrafish, Danio rerio.
S.P.
Dinesh-Kumar : molecular basis of host-pathogen
interactions in plants.
Douglas
Kankel : genetic and molecular analysis of
visual system development in Drosophila
Shirleen
Roeder : genetic and molecular analysis of
meiosis in yeast
William
Segraves : molecular and genetic analysis
of the insect steroid molting hormone ecdysone
in Drosophila.
Frank
Slack : Genetic control of developmental timing
in C. elegans.
Additional
Faculty with Interests in Genetics
Sidney
Altman : post-transcriptional RNA processing
as a means of gene regulation.
Ronald
Breaker : enzymatic DNA and in vitro evolution.
Thierry Emonet: Relating network architecture to biological function using computational modeling and experiments.
Martín
García-Castro : the origin of neural
crest cells.
Christine
Jacobs-Wagner : use of Caulobacter crescentus
to study genetic circuitry which controls cell
cycle.
Mark
Mooseker : molecular underpinnings of cytoskeletal
structure, motility and assembly.
Nicholas
Ornston : evolutionary relationships among
a set of genes which have coevolved within a single
cell line.
Michael
Snyder : molecular, cellular and genetic analysis
of cell structure and division in eukaryotes.
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NEUROBIOLOGY
The
interests of the neurobiology group concern developmental
neurobiology, the cell biology of axon guidance
and sensory physiology. The developmental neurobiologists
study factors controlling the assembly of neurons
into systems that generate specific neural patterns.
They use approaches combining electrophysiology
with embryology and tissue culture, genetics,
and neural regeneration. Development of the visual
and flight motor systems in Drosophila is studied
using genetics coupled with electrophysiology
and modern neuroanatomical techniques. Also studied
are the determination and differentiation of individual
neurons in the embryos of insects and how neuronal
diversity in the mammalian neocortex can be generated
through asymmetric division of neural progenitor
cells using gene targeting (knockout) approaches
in mice. Additional techniques include image intensification
and immunocytochemistry.
Development
of central neurons in lower vertebrates and insects
is studied to examine factors determining the
shape of nerve cells and the formation of specific
synaptic connections. All of these developmental
studies are aimed at understanding normal neural
development. In related studies, mechanisms of
axon guidance are investigated from a basic cell
biological perspective using a variety of biophysical
and optical techniques for investigating molecular
dynamics in living neurons maintained in cell
culture. These studies are aimed at understanding
how external molecular signals are transuded to
control neuronal growth cone motility and cytoskeletal
structure during axon elongation and path finding.
In general, these lines of investigation are also
relevant to questions of clinical importance,
dealing with abnormal neural development and neural
regenerationollowing injury. Central interests
in sensory physiology include photo and biochemistry
of visual pigments and retinoids, membrane turnover
and adaptation in arthropod photoreceptors, as
well as color vision of arthropods and birds.
A variety of techniques are used, including behavioral
analysis, micro-spectrophotometry, electrophysiology,
HPLC, and light and electron microscopy.
Faculty
having a Primary Affiliation with this Section
Paul
Forscher : molecular dynamics of guided axon
growth.
Martín
García-Castro : the origin of neural
crest cells.
Haig
Keshishian : analysis of neuromuscular development
in Drosophila.
Elke Stein
: the molecular mechanism that underlies neuronal
growth cone guidance.
Robert
Wyman : analysis of genes which control the
specificity of neuronal connectivity in Drosophila.
David
Wells : examination of the process of experience
dependent modification (or plasticity) of synapses
at the cellular and molecular levels.
Weimin
Zhong : Regulation of neural stem cells and
development of the mammalian neocortex.
Additional
Faculty with Interests in Neurobiology
John Carlson
: molecular and genetic analysis of olfactory
system in Drosophila.
Thierry Emonet: Relating network architecture to biological function using computational modeling and experiments.
Douglas
Kankel : genetic and molecular analysis of
visual system development in Drosophila.
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SPECIAL PROGRAM IN PLANT SCIENCES
Historically,
the Molecular, Cellular and Developmental Biology
Department has been especially strong in the areas
of plant developmental biology, physiology, and
systematics. In recent years, these strengths
have expanded into the areas of plant molecular
biology and genetics. The Special Program in Plant
Sciences reflects ongoing research and training
interests of the faculty in the molecular genetics
of flowering, the developmental biology of leaves,
the physiology of hormone action, the evolution
of plants, and a variety of other areas. Colleagues
in the Yale School of Forestry and Environmental
Studies, at the Cary Arboretum, and at the Connecticut
Agricultural Experiment Station contribute as
well to the seminars, graduate classes, workshops,
and field trips offered through the Program.
Faculty
with Interests in Plant Sciences
Xing-Wang
Deng : molecular mechanisms involved in light-triggered
regulation of growth and development in higher
plants.
Stephen
Dellaporta : molecular biology and
genetic utility of transposons in plants.
S.P.
Dinesh-Kumar : molecular basis of host-pathogen
interactions in plants.
Vivian
Irish : mechanisms that govern pattern formation
during plant development.
Timothy
Nelson : development of leaves.
Joel
Rosenbaum : assembly of cell organelles using
the flagella of Chlamydomonas as a model.
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SPECIAL PROGRAM IN BIOTECHNOLOGY
Many
recent research breakthroughs in the life sciences
are in the areas of biotechnology and genomics.
Faculty in the MCDB department are particularly
strong in these areas and many are associated
with research programs in Biotechnology companies.
Research topics encompass the development of nanosensors
and controlled nucleic acid enzymes, the generation
of transgenic animals and plants, small molecule
approaches to the analysis of gene function and
therapeutics, functional genomics, and the large
scale analysis of genomes and bioinformatics.
In addition to advanced topics that are critical
for excellence in the life sciences, courses in
Biotechnology, Genomics, and Bioinformatics are
available to students who wish to explore these
emerging areas.
Faculty with Interests in Biotechnology
Sidney Altman : knockout of gene function and functional genomics using ribonuclease P and external guide sequences
Ronald Breaker : creating new enzymes, molecular switches and genetic sensors using rational and combinatorial approaches for enzyme engineering.
Craig Crews : pharmaceutical target validation and small molecule-based exploration of cell biology.
Xing-Wang Deng : plant genetics and agribiotechnology.
Douglas Kankel : in collaboration with the Goodrich Corp., the development of new optical instruments for biochip analysis and for image acquisition and analysis.
Perry Miller : biomedical Informatics.
Nicholas Ornston : Manipulation of genes and metabolic pathways in bacteria.
Michael Snyder : functional genomics and the large-scale analysis of the yeast genome.
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DYNAMICAL MODELING AND REAL-TIME SYSTEMS ANALYSIS OF BIOLOGICAL SYSTEMS
The combination of numerical modeling together with the introduction of new methods imported from physics and engineering to probe the real-time dynamics of biological processes in vivo is bringing unprecedented predictive power to biology. It is now possible to build multi-scale dynamical models that relate molecular events inside single cells to the behavior of these cells as they interact with the environment and with each other. Dynamical models help focusing biological questions and targeting experiments, which in turn impose constraints on the models. Close interaction between experimental studies and modeling is key to success in this area and leads to the understanding of biological phenomena at the systems level.
Faculty with interests in Modeling
Thierry Emonet: Relating network architecture to biological function using computational modeling and experiments.
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