Follow McGill undergraduates around the ant lab to catch a glimpse of the volunteering experience, project opportunities, and rudiments of colony caretaking.
Video by Easton Houle with McGill's Media Relations Office.
Sunday, October 2, 2016
Saturday, February 27, 2016
The latest in gene regulation: a tribute to François Jacob
A conference titled "Genetic
Control of Development and Evolution" was held at the Pasteur Institute in
Paris in the autumn of 2015. The conference was a tribute to François Jacob for
his contribution to the study of gene regulation. With the help of QCBS funding
I was able to present my work at this conference.
My poster at the conference was
about endosymbiotic bacteria of ants of the genus Camponotus. We show
that the symbiont has driven major rearrangements in early egg development in
order to ensure stable endosymbiosis and transmission to the next generation. I
received excellent feedback at the conference that helped understand the data
in a better light.
The
conference was a broad update on gene regulation with reference to development
and evolution. Since Jacob and Monod a lot has been learnt about gene
regulation. Enhancers, the DNA elements that regulate the levels, timing and
spatial extent of gene expression was one of the major themes of the
conference. Many presenters showed how suboptimal binding sites make optimal enhancers
wherein weak binding sites and ‘half’ binding sites play a major role in
specificity of gene expression. Michael Levine of University of Berkley, uses
artificial enhancers generated by mutating transcription factor binding sites and
the spacing between them. He showed that native enhancers are weak in
comparison to artificially generated optimized strong enhancers. The native
enhancers are more specific, the stronger enhancers show mis-expression. Kenneth
Zaret of the University of Pennsylvania showed
that the recognition sites of Pioneer Factors (proteins that initiate release
of chromatin bound DNA making it active) are half of the recognition sites of
other transcription factors. This feature allows them to bind while allowing
the other side of DNA to remain bound to histones. This binding is not
sufficient and requires cooperativity and recruitment of other factors meaning
many of these bindings are abortive, hence improved specificity. Justin
Crocker from Howard Hughes Medical Institute - Ashburn, showed that in the shaven baby locus of Drosophila
the relative affinity and specificity of binding sites have an
inverse relationship implying that high
affinity binding sites may actually bind other genes and decrease specificity. When he changes a low affinity
site into a high affinity site it results in mis-expression. He also showed that in different species low
affinity binding sites are poorly conserved but are
functional in their respective contexts.
Marion Guéroult-Bellone from CNRS Montpellier showed how in vitro expression
assays are different from in vivo data in terms of levels of expression and reiterated
a known fact that spacing between binding sites regulates levels of expression.
François Spitz of EMBL Heidelberg showed that long
distance enhancers act dynamically activating several genes at the same time
where an appropriate TATA box is found at specific optimal distances from it. They use a reporter assay with
one enhancer and test for all expressed regions of
about 200 kbp region in both directions. If
the enhancer was flipped, it affected a reporter at a similar distance in the
opposite direction and resulted in a pattern mirroring its activity albeit only
when appropriate TATA boxes fell in its range of activity. This pattern of activation is
consistent with Topologically Associating Domains; meaning in 3D when a piece
of DNA falls in the vicinity of another piece of DNA they interact regardless
of their base-pair distance.
Another major theme of the
conference was chromatin remodeling for gene regulation. Edith Heard from Curie Institute in Paris
talked about mono-allelic gene expression in mammals.
Repression of the X-chromosome copies in females is well-known, she showed that
the X-chromosome that gets inactivated is randomly chosen such that two
females, even if identical twins, are different. In addition there are two
inactivation waves initiated by the Xist locus. The first one initiates early
during development and is maintained throughout development, this one is
initiated by the paternal locus. The second one is initiated at the
blastocyst stage that initially kicks in both alleles and then stabilizes to
persist in one allele inactivating it and not does not do so in the other
allele that stays active. This means that females are mosaics
due to random X-inactivation.
Gerarld Crabtree of Stanford talked about BAF
complexes that are polycomb repressor complexes (PRCs), which seem to be opposing both
PRC1 and PRC2 regulating both assembly and disassembly of chromatin. Bluma Lesch of Whitehead Institute Cambridge, USA showed
that developmental regulatory genes remain in the
poised state in the Germline in which they contain opposing histone states
H3K4me3 and H3K27me3 and are transcriptionally repressed. They continue in
the poised state in the gamete stage and this phenomenon is conserved from drosophila to
mammals.
A couple of interesting talks used
transcriptome sequence analysis to establish relatedness of cells or tissues.
Jacob Musser of EMBL Heidelberg used this method to test for relatedness
between dinosaurs feathers/scales and bird feathers using scales
on the feet of chickens. Principle component analysis of
transcriptome sequences of chicken feathers, chicken scales (of feet), chicken
nails, alligator scales, and alligator nails show
relatedness between bird feathers (not scales of feet) with alligator scales. Alexander Van Oudenaarden of Hubrecht
Institute, Utrecht has managed to find a way to separate single cells from the
bone marrow blood precursors and RNA sequence them one cell at a time to look
for shared expressed sequences. He then correlates their spatial proximity or
distance with the number of shared genes. This analysis confirms some of known
relationships in tissue precursors and points to spatial information in
precursor cells of bone marrow, a site for multiple stem cells. Shahragim Tajbakhsh
of Pasteur Institute – Paris showed that the
shared program for development of the craniofacial muscles and esophagus
muscles is not conserved in birds (birds do not need to chew and swallow). But
interestingly basal animals (Ciona being one) have this program. He
suggested that the birds might have lost it and more interestingly the
craniofacial muscle developmental program may actually have been coopted from
the esophageal program.
Patricia Wittkopp of University of Michigan does
experimental evolution in Drosophila and yeast
from different wild and lab sources. She has developed a
system with two different cis-alleles for the
same gene, each driving a different FP (red/yellow) in the same organism;
meaning the same trans-acting background driving two different cis-alleles.
Using this system she shows that there is higher cis-regulatory divergence in an evolving population, implying that cis regulatory divergence may be favored by natural
selection. She also uses induced C->T and G->A mutations and compares them with natural
occurring polymorphisms, which showed that natural polymorphism form a
subset of induced mutations in terms of noise indicating that noise is selected
against in natural selection.
Overall great fun and highly inspiring!
Monday, January 4, 2016
Epigenetic and Complex Social Behaviour
Subscribe to:
Posts (Atom)