Systems Biology Centre
Current Projects under IPCR

Advert link: 59238.

Post-doctoral Research associate in modelling in Biology Systems 59238-096.
Post-doctoral Research associate in Biology Systems)

A 2 yr PDRA post is available now (ideally starting asap or at least before April 2007) in the Systems Biology (EPSRC critical mass grant IPCR). Although priority will be given to  spatial modelling of the cytoskeleton (actin networks), candidates with appropriate skills will be considered for any of our other projects outlined below. Our projects are all highly interdisciplinary with strong links to experimental groups. Interested candidates should apply (full CV), stating in a covering letter their interests and outlining their previous work and skills.

Scientific queries can be addressed to David Rand (networks, systems biology) or Nigel Burroughs (Cytoskeleton, T cells), administrative queries to Brent Kiernan (the systems biology administrator).

Bead image
clock network
Actin network simulation: pushing a bead
Circadian clock of Neurospora crassa
(Young et al 2001)

The following projects are representative, additional information on some areas can be found on the IPCR website.

Priority project:

1. Cytoskeletal dynamic networks. We have developed a discrete simulation model (figure above) that qualitatively reproduces observed actin networks that are generated behind suitably treated polystyrene beads and some bacteria (listeria) in cell extracts and live cells. These so called comet tails propel the object. The simplest explanation for the movement is a racheting  mechanism where thermal/diffusive fluctuations are rectified by polymerisation of actin fibers at the surface of the obstacle.  However our simulations indicate stress is built up in the network suggesting that cooperative gel type characteristics are appearing in the network. A key aim is to capture essential network architecture properties in suitable continuum models (PDEs) and thus acheive macroscopic descriptions of the comet and associated networks. In a recent development we are investigating the role of a regulator (VASP) in modulating the balance of tethered to polymerising fibers that appears to dramatically affect the network structure. Models are a mix of stochastic differential equation (or Fokker-Planck equations) and continuum models (ODE, PDE and integro DE). Experience with continuum models (eg elasticity, liquid crystals), statistical mechanics, stochastic modelling and/or large scale simulation will be advantageous.

Other projects where we may appoint if suitable candidates apply.

2. Network inference: methodology and algorithm development. We have an extensive suite of algorithms for time series analysis of dynamical systems and the fitting of stochastic models using Markov chain Monte Carlo methods. The algorithms are based on Brownian bridges using hidden variable paths between time points. This has allowed us to quantify transcription kinetics through analysis of the fluctuations. This is a rapidly emerging area of great importance as fluorescent reporters become increasing more sophisticated and inferring parameters from such data is liable to dominate systems biology in the coming decade. The project will involving developing such methods to network inference and applying these on a variety of data sets from associated plant and eukaryotic cells (eg NFkB) projects.

3. Data integration: methodology and algorithm development. Data integration is a significant problem in systems biology. Key issues are the interface with bioinformatics data and data bases, and the inference on mixed data sets (eg micro arrays and proteomics). Developing suitable models and algorithms will be carried out. Experience with MCMC and bioinformatics will be advantageous.

4. Experimental design of differential bleaching Fluorescence experiments. Spatial aspects of cellular regulation can be measured using fluorescently tagged molecules. Bleaching, or the local distruction of the fluourescence can be used to unravel reaction kinetics and diffusion. We are analysing the identifiability of models given this type of data and using experimental design to examine how to optimise information. Experience with (Bayesian) experimental design, MCMC, sDEs and PDEs will be advantageous.

5. T cell signalling. An ongoing IPCR project with links to a model verification and analysis programme on the Natural Killer cell synapse.

6. Plant systems biology. In collaboration with HRI a number of projects are being initiated including leaf senescence (leaf death), plant-pathogen interactions and flowering. the projects are data driven using microarrays and associated high throughput gene/protein measurement techniques. the focus is the determine regulatory networks for these processes.

Candidates should have a relevant PhD (statistics, mathematics, physics, computer science or similar) and a skills appropriate for one or more of the areas, eg modelling in stochastic or deterministic systems, statistical simulation (such as MCMC), programming in C/C+, python or a similar language. Experience with biological applications is unnecessary but a willingness to  communicate with biologists is essential.

The computer environment includes linux clusters and IBM regatta systems.

Applications should be made to the Personnel Office, University of Warwick, Coventry CV4 7AL quoting Ref 59238-09 and include the following: 1) completed application form, 2) academic CV and 3) application letter outlining relevant experience and interests. Closing date 25th Oct 2006. The start date is flexible, ideally before April 07. Interviews late Oct/early Nov.

The appointment is funded by EPSRC/BBSRC.