Gene Expression in Development and Disease (GEDD@MSU)
Tuesday, September 24, 2013
Stopping HIV with a vaccine, and evolutionary insights
Last week the Department of Biochemistry and Molecular Biology at MSU featured Peter Kwong from the NIAID Vaccine Research Center. Hosted by Prof. Erik Martinez-Hackert, Dr. Kwong described how structural biologists are using "reverse engineering" to track the natural development of highly effective antibodies against the HIV1 virus in patients. The human immune system, over the course of 2-3 years, can eventually generate antibodies that target the sensitive sites on the envelope glycoprotein of the virus. Unfortunately for these patients, the development of these neutralizing antibodies occurs too late to put a halt to their infections, but if such antibodies could be produced by vaccination, they would likely block transmission. A tour-de-force of biochemistry, genomics, and immunology - maybe our investment in basic research will pay off to meet this continuing threat.
ASBMB Special Symposium hosted by GEDD July 25-28
"Nothing in biology makes sense except in the light of evolution" - an insight from fly geneticist Theodosius Dobzhansky that underscores how evolutionary insights permeate all aspects of biological research.
Faculty from the Michigan State University Gene Expression in Development and Disease Focus Group hosted a special symposium through the American Society of Biochemistry and Molecular Biology last July. A summary, first posted on Ian Dworkin's GenesGoneWild blog about this experience:
Faculty from the Michigan State University Gene Expression in Development and Disease Focus Group hosted a special symposium through the American Society of Biochemistry and Molecular Biology last July. A summary, first posted on Ian Dworkin's GenesGoneWild blog about this experience:
Evolution and Core Processes in Gene Regulation – some
“terminal” thoughts
Our symposium last week brought together some folks who
don’t regularly appear at the same conferences, including the structural
biologists and biochemists who’ve devoted a good part of the last 30 years to
unraveling the mechanisms of the central dogma – gene transcription, RNA
metabolism, and protein translation. The trend has been to identify the central
machinery, publish high-impact papers in single-word-title journals, and then
years later discover that things don’t necessarily work the same in all
contexts, organisms, developmental settings. Not surprising in eukaryotic
transcription, for instance, where the “basal machinery” comprises ~200
proteins. Zach Burton, conference
participant, refers to this complexity as a “molecular horror”, but from an
evolutionary perspective, it is also an opportunity.
With respect to tracking the changes inherent in functioning
of regulatory circuitry, we have more complete understanding of how bacterial
systems work. Nice presentations by Saeed Tavazoie
and Eduardo Groisman highlighted how easily
such systems can transition between regulatory states, with just a few genetic
changes in regulatory factors. Robert Landick and Seth Darst, in studies of E.
coli RNA polymerase, pointed out that this bacterium actually features a novel
outgrowth, an insertion of 188 amino acids that connects directly to the
conserved trigger loop in the catalytic site. Nobody knows what it is doing
there, but it is lineage specific, and mutations accumulate in this part of the
protein when cells are grown under nutrient limitation, suggesting a
short-circuit way to globally fiddle with gene expression.
Eukaryotic systems likewise have novel structures to their
core machinery; Lawrence Myers described the
gene amplification of Mediator subunits in Candida albicans that are linked to
pathogenicity, while Jean-Marc Egly pointed
out the pervasive effects of mutations in human Mediator and transcription
factor TFIIH. With eukaryotes, the importance of variability in core machinery
for generating important changes on the population or species level is obscure.
Studies such as those presented by Ian Dworkin
(host of this blog) and Aviv Regev showed
how we are able to identify numerous loci involved in genetic background
effects relating to development and immune function – but the overall
importance of pervasive impacts generated by changes in an RNA polymerase
subunit, for instance, vs. subtle changes in an enhancer is not clear. One
mystery I dropped on the conferees was the special features of the RNA Pol II
CTD found in Drosophila, but not other eukaryotes – a reflection of their
unique developmental gene expression, discussed by Melissa
Harrison and Julia Zeitlinger?
Aside from being mistaken once for Bill
Gates by a visitor from Shanghai while walking around the University of
Chicago, I was able to maintain my identity as a gene regulation specialist who
takes to heart Theodosius Dobzhansky’s mantra that “Nothing in Biology Makes
Sense Except in the Light of Evolution”. We will see how the combination of
biochemical detail and evolutionary perspective can propel us into a future
where gene regulation, in all its rich variation, makes sense. Many thanks to
Joan Geiling and Barbara Gordon from the ASBMB for making this an outstanding
conference!
Laconic Genes - David Arnosti with Gene Expression in Development and Disease (GEDD) at Michigan State University
Welcome to David Arnosti's blog at Michigan State University; I plan to comment on gene expression research, thoughts, and events that relate to research associated with Gene Expression in Development and Disease (GEDD) laboratories. I am motivated to launch this platform by the lively examples coming from the keyboards of my colleagues Titus Brown (http://ivory.idyll.org/blog/) and Ian Dworkin (http://genesgonewild.blogspot.com).
In this PC era (Post-Clapper; a reference to the propensity for anything that we upload to the cybersphere to end up anywhere), we will restrict our online commentary to the exciting world of research in gene expression, but rest assured that real bare-knuckle discussions happen at our weekly GEDD journal club that meets Friday afternoons.
In this PC era (Post-Clapper; a reference to the propensity for anything that we upload to the cybersphere to end up anywhere), we will restrict our online commentary to the exciting world of research in gene expression, but rest assured that real bare-knuckle discussions happen at our weekly GEDD journal club that meets Friday afternoons.
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