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Friday 2 March 2012

NCBS 2012 III: Divers

Two recurrent themes throughout the conference were 1) the limits of detection by sequence-only based methods, and 2) the apparent extreme complexity of the LECA, the Last Eukaryotic Common Ancestor. This was best illustrated by MC Field in his contribution entitled "Finding things that are not there - lessons at the nuclear envelope". He demonstrated that a combination of molecular biology experiments combined with bioinformatics, essentially structural predictions, were able to detect proteins that could not be detected by Blast searches. This was illustrated in the case of the nuclear pore complex of the trypanosome. Of course, in this case, extreme care has to be taken to discriminate the real signal from the noise. He extended his analysis from the nuclear pore complex to the transporter that ensure the transfer of the cargo through the nuclear envelope, the karyopherins. He showed that karyopherins are conserved and ancient, with at least 14 being most likely present in the LECA, again adding to the complexity of this elusive ancestor. Eventually concluding on the detection of things that are not there, he showed conclusive data about the presence of Lamin analogue in Trypanosome which was so far thought not to possess such an intranuclear protein (a work in press in PLoS Biology).

On a related theme, but different organism, Margaret 'Rossie' Robinson presented her last work on the detection of a new, the fifth, adaptor complex, AP5. The list of adaptor complex was thought to be complete, prompting some article title like 'Adaptins: the final recount' (MBoC 2001). It is genuine to wonder about how many such discovery are still awaiting out there.

MP Rout then presented his work on the structure of the nuclear pore complex by integrative modeling. I won't go back to the details of the work published in 2007, but they have pushed the limits of the method to achieve a model of a major building block of the complex, the so-called Nup84 complex, to a precision of ~1.5 nm. This amazing work has just been published in JCB (Fernandez-Martinez et al., 2012). The suggestions derived from the structure about a possible ancestral two fold symmetry at the core of the Nup84 complex was very inspiring and very much in line of the evolution of the nuclear pore complex and thus the protocoatomer hypothesis.
It is so beautiful that I can't resist to show you the inspiring figure taken from the publication
You can see the possible axis of duplication and the losses of the Nup85/Seh1 equivalent, as well as the reductive loss of Nup84 Nt-domain and Sec13 equivalent. Very inspiring.

Thursday 1 March 2012

NCBS 2012 IV and end: WF Martin

The meeting closed by a spectacular show by William Martin. Clearly deeply involved in what he was presenting, Bill started by a thorough recapitulation of all evolutionary scenarios that have been proposed for the origin of the eukaryotes, starting back in 1910, a century ago. The presentation was very comprehensive and Bill's own style ensured the audience of a great show.
Bill went on to present his latest work, including the Evolutionary network of gene in eukaryotes where they present a new method to solve the evolution of eukaryotic genes based on a network of lateral gene transfer. This is based on the fact the the origin of much eukaryotic genes shared with prokaryotes are found all over the tree of life. The conclusions stress the importance of archaea and of mitochondria in the origin of eukaryotic genes, and thus of the eukaryotes.
Bill ended up by discussing the Energetics of genome complexity according to which eukaryogenesis was only possible thanks to the release of the energetic constraints on the genome due to the internalization of the mitochondria. We were even treated by evolutionary movies during the questions. In conclusion, a very complete, entertaining and stimulating presentation by Bill Martin.

There were many other very interesting talks at the conference, including M Munson on the exocyst, Mara Duncan on the linear motifs interaction in the clathrin adaptors, M Bettencourt-Dias on the centrosome, and Frances Brodsky on clathrin, amongst many others. However, time and space constraints and the subject of this blog don't allow me to describe them here. Contributions from other attendees are welcome to present those talks not covered here or even to correct, comment or contribute to the discussion of those covered. The conference itself was actually preceded and followed by tutorials on Cell biology and immunology as well as on Evolutionary and informatic approaches.

All together, a very interesting conference. As I said, one of the most interesting and most interactive I have been to. Thanks a lot to Frances Brodsky, Satyajit Mayor and Mukund Thattai for the organization and ensuring its success. Words are circulating that there might be a follow up to this one, may be in Europe in two years. I will certainly be looking forward to it.

NCBS 2012 II: DP Devos

Damien Devos (EMBL, Heidelberg Germany, moving to the Center of Organismal Studies (COS) at the Heidelberg University) then presented his talk entitled "Microbiology's platypus". He first recapitulated the origin of the protocoatomer hypothesis, starting from a structural analysis of the nuclear pore complex; again highlighting the limits of sequences-only based methods. The first part of his talk ended with the importance of the membrane coat innovation as they form the core of the multi-protein complexes sustaining most divisions of the eukaryotic endomembrane system. As such, they must have been present in the LECA (him again) and probably in the ancestor of.
He then developed a method to use structure (since sequence search is limited, remember?) to search for this particular protein architecture and found it only in some of the PVC proteomes. Immunological characterization located such bacterial membrane coat-like proteins in the paryphoplasm of Gemmata cells. However, the differences of interpretation between him and the previous speaker, John Fuerst, became clear at that moment. Damien doesn't interpret the planctomycetes cell plan as different from the classical bacterial one, but just as an extension of it, when John interprets it as fundamentally different. An interesting discussion ensued and was followed over tee. Damien then presented his last work, where they reconstructed in three-dimensions various complete Gemmata cells. He showed a movie that first went through the tomogram of a cell, followed by the process of modeling the membranes and other features and ending with the final model. Unlike the previous speaker, no isolated compartments or even nucleoid envelope could be observed in this study. It would be interesting to pursue this analysis and resolve this issue. Damien then ended with his interpretation of the possible evolutionary connections between the PVC and the eukaryotic or archaeal features. He made the parallel between the special features found in PVC and the eukaryotes or archaea and the avian or reptilian ones found in the mammal platypus, hence the title of his talk.