Guilhem is going to be a speaker at the PLS Conference in Paris which is held between 26-28 May 2014. His title “PLS Path Modelling of the molecular origins of gene expression noise” has been accepted for oral presentation.
Congratulations to Dr. M. Madan Babu for getting the Protein Science Young Investigator Award this year. The Protein Science Young Investigator Award, named for the academic journal of the Society, recognizes an important contribution to the study of proteins by a scientist still in the early stages of an independent career.
In this essay, we discuss how regulatory elements within protein-coding regions (such as transcription factor binding) can influence codon choice and amino acid preference that are independent of protein structure or function. We discuss how there may be conflicts between codes and highlight that the redundancy in the genetic code might facilitate the existence of multiple overlapping regulatory codes within protein-coding regions of the genome. You can read the Perspective here.
Ben has been awarded the EMBL Interdisciplinary Postdoc (EIPOD) fellowship to work at EMBL-Heidelberg. Many congratulations to Ben!
Rob has been awarded the Marie Curie Fellowship to work between our group and that of Benjamin Blencowe’s lab in Toronto. Along with Marc Torrent and Natalia de Groot, that makes it three Marie Curie Fellows in the group. Many congratulations again Rob!
Promiscuity as a functional trait: intrinsically disordered regions as central players of interactomes
Because of their pervasiveness in eukaryotic genomes and their unique properties, understanding the role that ID (intrinsically disordered) regions in proteins play in the interactome is essential for gaining a better understanding of the network. Especially critical in determining this role is their ability to bind more than one partner using the same region. Studies have revealed that proteins containing ID regions tend to take a central role in protein interaction networks; specifically, they act as hubs, interacting with multiple different partners across time and space, allowing for the co-ordination of many cellular activities. There appear to be three different modules within ID regions responsible for their functionally promiscuous behaviour: MoRFs (molecular recognition features), SLiMs (small linear motifs) and LCRs (low complexity regions). These regions allow for functionality such as engaging in the formation of dynamic heteromeric structures which can serve to increase local activity of an enzyme or store a collection of functionally related molecules for later use. However, the use of promiscuity does not come without a cost: a number of diseases that have been associated with ID-containing proteins seem to be caused by undesirable interactions occurring upon altered expression of the ID-containing protein. The paper can be found here.
A methodology to infer gene networks from spatial patterns of expression – an application to fluorescence in situ hybridization images
The proper functional development of a multicellular organism depends on an intricate network of interacting genes that are expressed in accurate temporal and spatial patterns across different tissues. Complex inhibitory and excitatory interactions among genes control the territorial differences that explain specialized cell fates, embryo polarization and tissues architecture in metazoans. Given the nature of the regulatory gene networks, similarity of expression patterns can identify genes with similar roles. The inference and analysis of the gene interaction networks through complex network tools can reveal important aspects of the biological system modeled. Here we suggest an image analysis pipeline to quantify co-localization patterns in in situ hybridization images of Drosophila embryos and, based on these patterns, infer gene networks. We analyze the spatial dispersion of the gene expression and show the gene interaction networks for different developmental stages. Our results suggest that the inference of developmental networks based on spatial expression data is biologically relevant and represents a potential tool for the understanding of animal development. The paper can be found here.
Tilman Flock has been awarded the BIF Fellowship. The Boehringer Ingelheim Fonds awards PhD fellowships to outstanding junior scientists who wish to pursue an ambitious PhD project of approximately 3 years in basic biomedical research in an internationally leading laboratory.
Alternatively spliced protein segments tend to be intrinsically disordered and contain linear interaction motifs and/or post-translational modification sites. An emerging concept is that differential inclusion of such disordered segments can mediate new protein interactions, and hence change the context in which the biochemical or molecular functions are carried out by the protein. Since genes with disordered regions are enriched in regulatory and signaling functions, the resulting protein isoforms could alter their function in different tissues and organisms by rewiring interaction networks through the recruitment of distinct interaction partners via the alternatively spliced disordered segments. In this manner, the alternative splicing of mRNA coding for disordered segments may contribute to the emergence of new traits during evolution, development and disease. The paper by Marija Buljan et al can be found here.
In this work, we objectively compare known structures and reveal key similarities and differences among diverse GPCRs. We identify a consensus structural scaffold of GPCRs that is constituted by a network of non-covalent contacts between residues on the transmembrane helices. By systematically analysing structures of the different receptor–ligand complexes, we identify a consensus ‘ligand-binding cradle’ that constitutes the bottom of the ligand-binding pocket within the TM bundle. Furthermore, our comparative study suggests that the third TM helix has a central role as a structural and functional hub. The paper can be found here and the press release by MRC can be found here. Our work was No. 1 in Nature’s top 10 downloaded articles in February 2013, featured in Nature’s GPCR focus section and mentioned in the cover page.