Sunday, September 09, 2007

The biology of modular domains (day1 and morning of day2)

I am attending the 3rd (I think it is just the third) conference on modular protein domains. It is a small conference of just 80 people with a very nice environment for discussions. Given the nature of the conference I suspect that a lot of the talks will be about unpublished material so I will be light on the details since I have not personally asked people if I may post about their work.

In the first day of the conference on modular protein domains we had the opening lecture by Wendell Lim. It was a very light and interesting discussion of the evolution and engineering of signaling pathways. Lim started by discussing some interesting results coming from the sequencing of M. brevicollis, a unicellular choanoflagellate that is related to Metazoa and might provide some information about their evolution. It is a continuation of an analysis done by Nicole King and Sean B. Carroll that first identified a receptor tyrosine kinase in M. brevicollis, the first time one was identified outside of the Metazoa. The discussion was generally about the evolution of kinase signaling and how such a system of what Lim was naming "readers"~phospho-binding domains, "writers"~kinases and "erasers"~phosphotases can arise in evolution.
The second part of his talk was about the efforts to understand the evolutionary capacity of signaling networks by trying to engineer new or altered pathways. In this case the focus was on how with few components and small changes in these components it is possible to shape the dynamic responses of signaling networks.

Morning session of the second day

Synthetic biology
The Synthetic Biology sessions started off with a talk by David Searls on "A linguistic view of modularity in macromolecules and networks" (that was not very related to synthetic biology but nevertheless interesting). Searls detailed his views on the analogies between linguistics and biology. Here is a recent review by Mario Gimona on this analogy. At the protein level we could think of sequence, structure, function and protein role as similar to lexical, syntatic, semantic and pragmatic levels of linguistic analysis:

(Image reproduced with permission)

The general idea of building these bridges over topics is to be able to take existing methods and discussions from one side to the other (see review).

The second talk was by Kalle Saksela and again it had little to do with synthetic biology. Saksela's group is working on high-throughput interaction mapping for human SH3 domains against full proteins (human and viral proteins). They mentioned their progress in expressing and analyzing a subset of these interactions. He mentioned an interesting example were the Nck and Eps8L1 SH3 domain binding site in CD3epsilon overlaped with an ITAM motif such that the phosphorylation of the ITAM motif abolished binding by the SH3 domains. It is a nice example of signaling mediated by different types of peptide binding domains (see paper for details).

The third talk was by Rudolf Volkmer. He gave a short talk on a library of coiled coil proteins. The library contains many single mutant variants of the GCN4 leucine-zipper sequence. They then tested pairs mutants for heterodimerization by SPOT assays. Aside from a extending the knowledge of these domain family the library can also be used know as a toolkit of binding domains for synthetic biology (the work is already published).

The final talk on this panel was from Samantha Sutton from the Drew Endy lab. This was more like what one would expect from a synthetic biology talk . Samantha Sutton is interested in developing what she calls Post Translational Devices, general abstract devices that can regulate the post translational state of proteins in a predictable fashion. She has a page in OpenWetWare detailing her thoughts on this.

The second panel in the morning was about In silico computational methods.
Cesareni presented their ongoing efforts to experimentally determine human SH3 and SH2 interactions with spotted peptides. He then showed how this data can be used to search for examples where there is overlapping recognition by different domain types. The work is similar in methodology to the paper published by Christiane Landgraf and colleagues in PLoS Biology but know using two domain families and the human proteome.

Vernon Alvarez from AxCell Biosciences, gave a talk about a proprietary database called ProChart (that I cannot find online) containing many domain-peptide interactions tested by the company. He was basically promoting the database for anyone interested in collaborations.

The third talk was by Norman Davey author of SLIMDisc a linear motif discovery method. He is trying to improve their method, mostly by improving the statistics.

I gave the second short talk of the session. It was on predicting binding specificity of peptide binding domains using structural information. It is basically a continuation of some of the work I mentioned before here in the blog about the use of structures in systems biology but know applied to domain-peptide interactions.