November Day 1

 

November Day 2

 

 

Abstracts

 

Bahram Houchmanzadeh

Laboratoire de Spectrométrie Physique, Université Joseph Fourier, Grenoble.

Title : Stochastic clustering in ecological systems.

 

Abstract :

Random processes can have important and counter intuitive consequences in living systems. The role of fluctuations in cellular processes has been the focus of researchers during the last decade. Here, we'll give an example of the importance of these processes at a higher scale, i.e. the ecosystem. The random processes under consideration here are birth, death and random motions and they provoke clusters in the spatial distributions of species in an ecosystem.

 

 

Pieter Rein ten Wolde

FOM Institute for Atomic and Molecular Physics, Amsterdam, The Netherlands.

Title : The importance of spatio-temporal correlations in gene regulation and signal transduction networks.

 

Abstract :

Gene regulation networks and signal transduction pathways are the central processing units of life. In the modelling of these networks, it is often assumed that the system can be described as a well-stirred reactor in which the components are uniformly distributed at all times. We have recently developed a new algorithm, called Green's Function Reaction Dynamics (GFRD), which makes it possible to simulate biochemical networks at the particle level in time and space. The scheme is highly efficient and makes it possible to simulate biological systems at the relevant biological length and time scales. In this talk, I will discuss the application of GFRD to gene expression and signal transduction. The simulations reveal that spatial fluctuations of gene regulatory proteins due to diffusion can drastically enhance the noise in gene expression. Moreover, we show that spatio-temporal correlations can strongly change the macroscopic behaviour of signal transduction pathways: in a system that is spatially uniform on average, spatio-temporal correlations between enzyme and substrate molecules can lead to loss of ultrasensitivity and bistability. 

 

 

Maria C. Romano

Aberdeen University.

Title : Traffic jams in the cell: lost in translation.

 

Abstract :

Gene expression begins with the synthesis of an mRNA transcript, which is then translated into protein by the ribosome. The properties of a cell or tissue are conferred both by the identities of the synthesised proteins made in this way, and by their quantities (the proteome). Present day postgenomic technologies deliver an accurate picture of the complete mRNA set of a cell, but are much less able to reliably and quantitatively define the proteome. The ability to predict how efficiently any given mRNA can be translated into protein is thus an essential prerequisite to develop a systemwide understanding of cell physiology. We have developed a stochastic model of translation elongation that predicts the protein production rate for any given mRNA, based on the complex dynamics of ribosome traffic on the mRNA. We have derived numerical and analytical results for the current of ribosomes on the mRNA, where to each codon a different hopping probability has been associated. We show that the queueing of the ribosomes behind a slow codon can lead to a first-order phase transition, and derive analytical expressions for the configuration of slow codons for this to happen. We furthermore show that the first-order phase transition, uncovered in this work, is the process responsible for the classification of the proteins having different biological functions, namely, ribosomal and non-ribosomal ones.

 

 

Ana Pombo

Genome Function Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK.

Title : Poised transcription complexes in epigenetics and genome function.

 

Abstract :

Embryonic stem (ES) cells are characterised by their pluripotency and ability to self-renew. Many silent developmental regulator genes display ‘bivalent’ histone modifications that are associated with both silent and active chromatin and are regulated by Polycomb repressor complexes (PRC1 and PRC2). We have recently identified the presence of RNA polymerase II (RNAPII) complexes at a small number of bivalent genes with an unusual poised structure. Poised RNAPII complexes are detected at bivalent genes in amounts comparable to active genes, and are associated with phosphorylation of Ser5 residues of the C-terminal domain of RNAPII at promoters and through coding regions, with no detectable phosphorylation on Ser2 residues. Poised RNAPII complexes transcribe through coding regions of silenced genes, and transcripts undergo limited splicing. We are currently in the process of mapping different phosphorylated forms of RNAPII in mouse ES cells genome-wide by ChIP-seq and ChIP-chip. Our results suggest a mechanism of Polycomb silencing that acts downstream of transcription initiation and involves reduced processivity of elongating RNAPII complexes and poor coupling between RNA synthesis and processing.