ERC FUNDED PROJECTS

MAL: an actin-regulated SRF transcriptional coactivator Recent years have seen a revitalised interest in the role of actin in nuclear processes, but the molecular mechanisms involved remain largely unexplored. We will elucidate the molecular basis for the actin-based control of the SRF transcriptional coactivator, MAL. SRF controls transcription through two families of coactivators, the actin-binding MRTFs (MAL, Mkl2), which couple its activity to cytoskeletal dynamics, and the ERK-regulated TCFs (Elk-1, SAP-1, Net). MAL subcellular localisation and transcriptional activity responds to signal-induced changes in G-actin concentration, which are sensed by its actin-binding N-terminal RPEL domain. Members of a second family of RPEL proteins, the Phactrs, also exhibit actin-regulated nucleocytoplasmic shuttling. The proposal addresses the following novel features of actin biology: ¿ Actin as a transcriptional regulator ¿ Actin as a signalling molecule ¿ Actin-binding proteins as targets for regulation by actin, rather than regulators of actin function We will analyse the sequences and proteins involved in actin-regulated nucleocytoplasmic shuttling, using structural biology and biochemistry to analyse its control by changes in actin-RPEL domain interactions. We will characterise the dynamics of shuttling, and develop reporters for changes in actin-MAL interaction for analysis of pathway activation in vivo. We will identify genes controlling MAL itself, and the balance between the nuclear and cytoplasmic actin pools. The mechanism by which actin represses transcriptional activation by MAL in the nucleus, and its relation to MAL phosphorylation, will be elucidated. Finally, we will map MRTF and TCF cofactor recruitment to SRF targets on a genome-wide scale, and identify the steps in transcription controlled by actin-MAL interaction.

1 889 995 €

Start date: 2011-10-01, End date: 2017-09-30

It has long been understood that genes contribute to phenotypes that are then the basis of selection. However, the nature and process of this relationship remains largely theoretical, and the relative contribution of change in gene expression and coding sequence to phenotypic diversification is unclear. The aim of this proposal is to fuse information about sexually dimorphic phenotypes, the mating systems and sexually antagonistic selective agents that shape sexual dimorphism, and the sex-biased gene expression patterns that encode sexual dimorphisms, in order to create a cohesive integrated understanding of the relationship between evolution, the genome, and the animal form. The primary approach of this project is to harnesses emergent DNA sequencing technologies in order to measure evolutionary change in gene expression and coding sequence in response to different sex-specific selection regimes in a clade of birds with divergent mating systems. Sex-specific selection pressures arise in large part as a consequence of mating system, however males and females share nearly identical genomes, especially in the vertebrates where the sex chromosomes house very small proportions of the overall transcriptome. This single shared genome creates sex-specific phenotypes via different gene expression levels in females and males, and these sex-biased genes connect sexual dimorphisms, and the sexually antagonistic selection pressures that shape them, with the regions of the genome that encode them. The Galloanserae (fowl and waterfowl) will be used to in the proposed project, as this clade combines the necessary requirements of both variation in mating systems and a well-conserved reference genome (chicken). The study species selected from within the Galloanserae for the proposal exhibit a range of sexual dimorphism and sperm competition, and this will be exploited with next generation (454 and Illumina) genomic and transcriptomic data to study the gene expression patterns that underlie sexual dimorphisms, and the evolutionary pressures acting on them. This work will be complemented by the development of mathematical models of sex-specific evolution that will be tested against the gene expression and gene sequence data in order to understand the mechanisms by which sex-specific selection regimes, arising largely from mating systems, shape the phenotype via the genome.

1 350 804 €

Start date: 2011-01-01, End date: 2016-07-31

Iridescence is a form of structural colour which changes hue according to the angle from which it is viewed. Blue iridescence caused by multilayers has been described on the leaves of taxonomically diverse species such as the lycophyte Selaginella uncinata and the angiosperm Begonia pavonina. While much is known about the role of leaf pigment colour, the adaptive role of leaf iridescence is unknown. Hypotheses have been put forward including 1) iridescence acts as disruptive camouflage against herbivores 2) it enhances light sensing and capture in low light conditions 3) it is a photoprotective mechanism to protect shade-adapted plants against high light levels. These hypotheses are not mutually exclusive: each function may be of varying importance in different environments. To understand any one function, we need a interdisciplinary approach considering all three potential functions and their interactions. The objective of my research would be to test these hypotheses, using animal behavioural and plant physiological methods, to determine the functions of leaf iridescence and how the plant has adapted to the reflection of developmentally vital wavelengths. Use of molecular and bioinformatics methods will elucidate the genes that control the production of this potentially multifunctional optical phenomenon. This research will provide a pioneering study into the generation, developmental impact and adaptive significance of iridescence in leaves. It would also answer questions at the frontiers of several fields including those of plant evolution, insect vision, methods of camouflage, the generation and role of animal iridescence, and could also potentially inspire synthetic biomimetic applications.

1 118 378 €

Start date: 2011-01-01, End date: 2016-07-31

The advent of high-power laser systems in the past two decades has opened a new field of research where astrophysical environments can be scaled down to laboratory dimensions, yet preserving the essential physics. This is due to the invariance of the equations of ideal magneto-hydrodynamics (MHD) to a class of self-similar transformations. In this proposal, we will apply these scaling laws to investigate the dynamics of the high Mach number shocks arising during the formation of the large-scale structure of the Universe. Although at the beginning of cosmic evolution matter was nearly homogenously distributed, today, as a result of gravitational instability, it forms a web-like structure made of filaments and clusters. Gas continues to accrete supersonically onto these collapsed structures, thus producing high Mach number shocks. It has been recently proposed that generation of magnetic fields can occur at these cosmic shocks on a cosmologically fast timescale via a Weibel-like instability, thus providing an appealing explanation to the ubiquitous magnetization of the Universe. Our proposal will thus provide the first experimental evidence of such mechanisms. We plan to measure the self-generated magnetic fields from laboratory shock waves using a novel combination of electron deflectometry, Faraday rotation measurements using THz lasers, and dB/dt probes. The proposed investigation on the generation of magnetic fields at shocks via plasma instabilities bears important general consequences. First, it will shed light on the origin of cosmic magnetic fields. Second, it would have a tremendous impact on one of the greatest puzzles of high energy astrophysics, the origin of Ultra High Energy Cosmic Rays. We plan to assess the role of charged particle acceleration via collisionless shocks in the amplification of the magnetic field as well as measure the spectrum of such accelerated particles. The experimental work will be carried both at Oxford U and at laser facilities.

1 119 690 €

Start date: 2010-12-01, End date: 2015-11-30