Modular protein domains (an overdue wrap-up)

I did not even cover 1/3 of the Module Protein Domain workshop in my previous blog post. I will not attempt to do it know after so much time. The organizers were clearly concerned about keeping the information withing the participants so I will just post some of the general impressions that I took from the meeting.

Specificity profiling in high gear
There were several sessions dedicated to particular protein domains (SH3, SH2 and PDZ in particular) and for all of these there are several projects under way (or mostly completed) to determine the binding specificity of a large number of these domains (although in different species) using either phage display, spotted peptides and other methods. We should project ahead and start planning what to do with this information. How to combine this to predict pathways and pathway models with dynamical information. The work of Rune Linding is a a very good start at this (see NetworKIN).
Given that the methods are set up I suspect that the emphasis might shift now on exploring the evolution of binding specificities and the impact of disease causing mutations (i.e. profiling binding specificities of domain variants).

Good integration of different methods
Compared to the same meeting two years ago I had an impression that there was a better integration of different approaches (biochemical, structural, computational, etc). A particularly good example was the work of Michael B. Yaffe. There were plenty of structural talks (probably a bit too much) but I found particularly interesting the work of Ivan Dikic that presented extensive novel work on ubiquitin binding domains and Charalampos Kalodimos that presented his lab's work on potential functional roles of proline isomerization (Pubmed).
The computational part was well represented too and it was fun to see again Gary Bader and to get to know Philip Kim.

I hope to be there again in two years time to see how the field changed.

Bio::Blogs #15 - call for submission

Since there were no volunteers :) I will be hosting the 15th edition of Bio::Blogs here in the blog. I will be gathering some posts from around the web on bioinformatics and other science related topics from the last month and will post about in on the 1st of October. Suggestions are more than welcome. Please email any links to interesting blog posts to bioblogs at gmail dot com.

On a personal note, I have defended my PhD :). This mostly explains the low volume blogging.

The ephemeral journal II

(via Deepak) Earlier this month I posted about how re-grouping of content after publication could be used to foster the creation of more focused online scientific communities. My impression is that these "places" could more easily attract a group of people of similar interests that would more likely engage in discussions, in contrast to a place like PLoS ONE that covers way to many topics.

There are several names for these groupings (Nature/BMC gateways, Nature Reports, a topics page) and PLoS came out with another one - Hub. They launched a re-grouping of content focused on Clinical Trials that they call PLoS Hub for Clinical Trials. It is built on Topaz so it has everything that PLoS ONE has (comments, ratings, trackbacks,etc).

They mention in the home page of this Hub that they plan to in the future also "feature open-access articles from other journals plus user-generated content". I suspect that they could go even a bit further on this and give more control to the users for the creation of content for the Hubs and even to create new Hubs. One thing that I like in traditional journals that also creates a feeling of identity and community is the more personal news and views and editorials. PLoS could commission/invite scientists/bloggers to help create this type of content for their Hubs. This would be something like a community blog centered on this Hubs' research.

Once upon a time (before Digg if I remember right), we tried to do this in Nodalpoint. For a while we had a queue from bioinformatic related journals that we could vote on to upgrade it to the front page of the blog. At the time it did not work very well because of lack of users and participation but it in essence it was not very different from what the publishers are trying to do now. Maybe we could try it again :).

Vote for your favorite life science blogs

(via Science Hacker and Postgenomic) The Scientist wants to compile a list of life science blogs that people enjoy reading as a reference. It is really not a good question to ask since there are so many different fields and styles of writing.

More on open science

I am still catching up with a backlog of feeds and e-tocs but I just noticed that Benjamin Good posted his manuscript on E.D. in Nature Precedings. I wend back to his post where he first presented the manuscript to have a look at the comments and there is a nice discussion going on there. It is a good example of the usefulness of posting our work online. There might be still few people knowledgeable about particular interests to gain very good feedback in all areas but this will tend to grow with time.

Michael Barton from Bioinformatics Zen started a new blog to use as an open science notebook about his own research.

I have a mini project in mind about the evolution of domain families that I will start describing and working on here in the blog soon.

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.

The Biology of Modular Protein Domains

From tomorrow on I will be in Austria for a small conference on the biology of protein domains. I might post some short notes about the meeting in the next few days. I'll get a chance to present some of the things I have been working on about the prediction of domain-peptide interactions from structural data.

Here is one of these modular protein domains, an SH3 domain, in complex with a peptide:
The very short summary of it is that it is possible to take the structure of one of these domains in complex with a peptide (ex: SH3, phospho binding domains, kinases, etc) and predict their binding specificity. To some extent it is also possible to take a sequence, obtain a model (depends on structural coverage) and determine its specificity. I'll talk more about the details (hopefully) soon.

Scifoo Lives On: Definitions in Open Science

I am having a quick look at the session Definition in Open Science, going on in Second Nature (I'm Duriel Akula in Second Life). The place looks very different from the first time I had a look around the island. It is full of posters and other interesting material. Here is a picture as some of the first people started gathering:


Live coverage of the event by Berci (also in the picture).