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Selman A. Wakman award for Carol A. Gross
1. Selman A. Waksman award
for Carol A. Gross
M. Kokila
Ph. D., Research Scholar
Department of Microbiology
Faculty of Science
Annamalai University
AUM to PET
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2. Carol A. Gross was post doctoral researcher and then faculty
member at the University of Wisconsin, Madison.
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3. Carol A. Gross is a Professor of cell and tissue biology at the
University of California San Francisco (UCSF).
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4. She is very active in the graduate programs, especially
teaching and mentoring students.
In most of her research career, she used molecular
approaches to study transcriptional regulation and stress
responses in the bacterium E. coli.
Recently the laboratory has switched to functional
Genomics, where she is team are developing high throughput
phenotyping approaches to rapidly discover gene function
and cellular networks. 4
5. Her Work:
Transcriptional regulation
Controlling the rate of gene transcription for
example by helping or hindering RNA polymerase binding
to DNA.
Transcription
The process of making RNA from a DNA template
by RNA polymerase
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6. Transcription factor
A substance, such as a protein, that contributes to
the cause of a specific biochemical reaction or bodily
process.
Promoter
A region of DNA that initiates transcription of a
particular gene
Sigma factor
Specialized bacterial co-factors that complex with
RNA Polymerase and encode sequence specificity
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7. Coactivator
A protein that works with transcription factors
to increase the rate of gene transcription
Corepressor
A proteins that work with transcription factors
to decrease the rate of gene transcription
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9. • Selman A. Waksman award was first awarded in 1968. A
prize of $20,000 that is presented to recognize a major
advance in the field of Microbiology
• In 2011 Carol A. Gross has been awarded Selman A.
Waksman Award in Microbiology by the U.S. National
Academy of Sciences. For “Her pioneering studies on
mechanisms of gene transcription and its control, and for
defining the roles of sigma factors during homeostasis and
under stress.” 9
10. Research Interests:
• Research interests are Transcription regulation
• Heat shock control and global control networks.
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11. Transcriptional regulation
In Molecular biology and genetics, transcriptional
regulation is the means by which a cell regulates the
conversion of DNA to RNA (transcription) there by
orchestrating gene activity.
A single gene can be regulated in a range of ways, from
altering the number of copies of RNA that are transcribed,
to the temporal control of when the gene is transcribed.
This control allows the cell or organism to respond to a
variety of intra- and extra cellular signals and thus mount a
response.
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13. Some examples of this include producing the mRNA that
encode enzymes to adapt to a change in a food source,
producing the gene products involved in cell cycle specific
activities and producing the gene products responsible for
cellular differentiation in multicellular eukaryotes, as studied
in evolutionary developmental biology.
The regulation of transcription is a vital process in all living
organisms. It is orchestrated by transcription factors and other
proteins working in concert to finely tune the amount of RNA
being produced through a variety of mechanisms.
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14. Prokaryotic organisms and Eukaryotic organisms have
very different strategies of accomplishing control over
transcription.
Most importantly is the idea of combinatorial control, which
is that any given gene is likely controlled by a specific
combination of factors to control transcription.
This combinatorial nature extends to complexes of far more
than two proteins, and allows a very small subset (less than
10%) of the genome to control the transcriptional program
of the entire cell.
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15. Transcriptional Regulation In Prokaryote:
Much of the early understanding of transcription
came from Prokaryotic organisms, although the extent and
complexity of transcriptional regulation is greater in
eukaryotes. Prokaryotic transcription is governed by three
main sequence elements:
1. Promoters
2. Operators
3. Positive control elements that bind to DNA and incite
levels of transcription.
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17. Promoter:
In genetics, a promoter is a region of DNA that leads
to initiation of transcription of a particular gene. Promoters are
located near the transcription start sites of genes, upstream on
the DNA (towards the 5 region of the sense strand). Promoters
can be about 100–1000 base pairs long.
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18. Operator:
In genetics, an operon is a functioning unit
of DNA containing a cluster of genes under the control of a
single promoter The genes are transcribed together into
an mRNA strand and either translated together in the cytoplasm, or
undergo splicing to create mono cistronic mRNAs that are
translated separately, several strands of mRNA that each encode a
single gene product.
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19. Complexity of generating a eukaryotic cell carries with an
increase in the complexity of transcriptional regulation.
Eukaryotes have three RNA polymerases, known as Pol I, Pol II,
and Pol III. Each polymerase has specific targets and activities,
and is regulated by independent mechanisms.
There are a number of additional mechanisms through which
polymerase activity can be controlled. These mechanisms can be
generally grouped into three main areas.
Transcriptional Regulation In Eukaryote:
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21. Transcription factor
In molecular biology a transcription factor (TF)
or (Sequence-specific DNA-binding factor) is a protein that
controls the rate of transcription of genetic information
from DNA to messenger RNA, by binding to a specific DNA
sequence.
Groups of TFs function in a coordinated fashion to direct cell
division, cell growth, and cell death throughout life cell
migration and organization (body plan) during embryonic
development and intermittently in response to signals from
outside the cell, such as a hormone.There are up to 1600 TFs in
the human genome. 21
23. Carol A Gross areas of Expertise
1. Virology & Microbial Pathogenesis
2. Human Genetics
3. Regulation of Gene Expression
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24. Primary Thematic Area: Virology & Microbial Pathogenesis
Virology and Microbial Pathogenesis are intrigued by how
microbes manipulate their multi-cellular hosts to cause disease.
The resultant research programs provide an unprecedented
opportunity to influence global health. World-wide, infectious
diseases are the leading cause of death, with simple diarrheal
illness, malaria and TB leading the pack.
.
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25. Other infectious diseases, including AIDS, are a major
impediment to economic advancement in the third world. The
identification of new pathogens, the re-emergence of old
pathogens and the increasing incidence of antibiotic resistance
reflect the globalization of humanity and microbes.
New well as old pathogens can rapidly move great distances
and establish footholds in new niches. Strategies for the
prevention, treatment and control of infectious diseases require
fundamental bench research that takes advantages of rapid
advances in genomics, proteomics, cell biology, and
immunology.
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26. Secondary Thematic Area: Human Genetics
Human genetics is the study of inheritance as it occurs
in human beings. Human genetics encompasses a variety
of overlapping fields including classical genetics,
cytogenetics, molecular genetics, biochemical genetics,
genomics, population genetics, developmental
genetics, clinical genetics and genetic counseling.
Genomics Population Genetics 26
27. Genes are common factor of the qualities of most human-
inherited traits. Study of human genetics can answer
questions about human nature, can help understand diseases
and the development of effective disease treatment, and help
us to understand the genetics of human life.
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28. Gene expression is the process by which information from
a gene is used in the synthesis of a functional gene product.
These products are often proteins, but in non-protein coding
genes such as transfer RNA or small nuclear RNA genes, the
product is a functional RNA.
The process of gene expression is used by all known as life
eukaryotes (including multicellular organisms) prokaryotes
(bacteria and archaea), and utilized by viruses to generate
the macromolecular machinery for life.
Regulation of Gene Expression
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30. Regulation of transcription in cancer:
In vertebrates, the majority of gene promoters contain a CpG
island with numerous CpG sites When many of a gene's promoter
CpG sites are Methylated the gene becomes silenced. Colorectal
cancers typically have 3 to 6 driver mutations and 33 to
66 hitchhiker or passenger mutations.
CpG island& CpG Sites
Methyl Groups
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31. Transcriptional silencing may be more importance than
mutation in causing progression to cancer. For example, in
colorectal cancers about 600 to 800 genes are transcriptionally
silenced by CpG island methylation (see regulation of
transcription in cancer).
Transcriptional repression in cancer can also occur by
other epigenetic mechanisms, such as altered expression
of microRNAs. In breast cancer, transcriptional repression
of BRCA1 may occur more frequently by over-expressed
microRNA-182 than by hyper methylation of the BRCA1
promoter (see Low expression of BRCA1 in breast and
ovarian cancers). 31
Her research focus on transcriptional regulation in bacteria
A typical prokaryotic cell contains a cell membrane, chromosomal DNA that is concentrated in a nucleoid, ribosomes, and a cell wall. Some prokaryotic cells may also possess flagella, pili, fimbriae, and capsules.