End of the year with chemogenomics

Taken from jurvetson at:
www.flickr.com/photos/jurvetson/3156246099/

Around this time of the year it is customary to make an assessment of the year that is ending and to make a mental list of things we wish for in the year ahead. Here is my personal (but work related :) take on this tradition.

My academic year ended with the publication of two works related to chemogenomics. Chemogenomics or chemical genomics tries to study the genome-wide response to a compound. Usually, collections of knock-outs or over-expression of large number of genes are grown in the presence or absence of a small molecule to assess the fitness cost (or advantage) of that perturbation to the drug response. This is what was done in these two works.

In the first one, Laura Kapitzky (a former postdoc colleague in the lab) used a collection of KO strains both in S. cerevisiae and S. pombe to essay for the growth in the presence of different compounds. The objective was to study the evolution of the drug response in these distantly related fungi. In line with what was previously observed in the lab for genetic-interactions and kinase-substrate interactions we found that drug-gene functional interactions were poorly correlated across these two species. Perhaps one interesting highlight from this project was that we could combine data from both fungi to improve the prediction of the mode-of-action of the compounds.

The second project, in which I was only minimally involved in, was a similar chemogenomic screen but at a much larger scale. As the tittle implies "Phenotypic Landscape of a Bacterial Cell" (behind paywall), is a very comprehensive study of the response of the E.coli whole knock-out library against an array of compounds and conditions. Robert, Athanasios and other members of the Carol Gross lab did an amazing job of creating this resource and picking some of the first gems from it.

Something that I wanted to highlight here was not so much what was discovered but what I was left wanting. These sort of growth measurements tell us a lot about drug-gene relationships. We also have a growing knowledge of how genes genetically interact either by similar growth measurements in double-mutants or by predictions (as in STRING). These should allow us then to make prediction about how drugs interact. If two drugs can act in synergy to decrease the growth of a bug we should be able to rationalize that in terms of drug-gene and gene-gene interactions. I find this is a very interesting area of research. Naively these sort of data should allow us to predict drug combinations that target a specific species (i.e. pathogen) or diseased tissue but not the host or the healthy tissue. Here is a scientific wish for 2011, that these and other related datasets will give us a handle on this interesting problem.

As for the future, I am entering the final year of my current funding source (thank you HFSP) so my attention is turning into finding either some more funds or another job. I will continue working on the evolution of signalling systems, in particular trying to find the function of post-translational modifications (aka P1). Unfortunately the project failed as an open science initiative, something that I have mostly given up for now. I think the main reason it didn't work was because of lack of collaborators of similar (open) interests and non-overlapping skill sets as Greg and Neil were discussing in the Nodalpoint podcast a while ago.

See you all in 2011 !

The GABBA program

I was recently in the annual meeting of my former PhD program, the GABBA program, a Graduate Program in Areas of Basic and Applied Biology in Portugal. I realized that I never blogged about the Portuguese PhD programs and I thought I would share with you their somewhat unusual concept.

Like in other PhD programs, GABBA students start by having courses during the first semester of the program. The semester is divided into week long courses in different subjects (think Cell-Cycle, Development, etc) with invited teachers. What is different from most other programs I know of is that students then get to use their scholarship to do their research projects anywhere in the world. GABBA students get payed to do their research in any lab that accepts them, no strings attached. No return clause, not even a requirement to inform the program of research progress. There is an annual meeting where students (and alumni) get to go to Portugal to present their work but no one is obliged to go. It is also a nice opportunity to exchange tips and in some cases even start collaborations.

The annual meeting is always organized around Christmas time so most people end up going. I kept going to the meetings after finishing my PhD mostly because I enjoy seeing the people but also because of the cool science. As you can imagine, everyone is scattered around the world in very nice labs doing research in all sort of different biomedical related subjects. This year there were a lot of talks about stem cells and an unusually high number of neurobiology related work. Some cool research of note for me were for example the work of Martina Bradic (Borowsky lab at NYU) about the convergent evolution of blind cave fish and the talk by Andre Sousa (Sestan Lab at Yale) on the transcriptional profiling of human brain regions during development (http://hbatlas.org/).

The GABBA program takes international students as well but they are typically asked to do their research in Portugal. The applications are usually around June so keep an eye out if you are interested in applying. Have a look at the admissions page for more information.