Computational Biology Support: RECOMB Conference Series (Conference Support)

This funding was support for student and postdoctoral attendance at the Annual Recomb Conference from 2001 to 2005. The RECOMB Conference series was founded in 1997 to provide a scientific forum for theoretical advances in computational biology and their applications in molecular biology and medicine. The conference series aims at attracting research contributions in all areas of computational molecular biology. Typical, but not exclusive, the topics of interest are: Genomics, Molecular sequence analysis, Recognition of genes and regulatory elements, Molecular evolution, Protein structure, Structural genomics, Gene Expression, Gene Networks, Drug Design, Combinatorial libraries, Computational proteomics, and Structural and functional genomics. The origins of the conference came from the mathematical and computational side of the field, and there remains to be a certain focus on computational advances. However, the effective use of computational techniques to biological innovation is also an important aspect of the conference. The conference had a growing number of attendees, topping 300 in recent years and often exceeding 500. The conference program includes between 30 and 40 contributed papers, that are selected by a international program committee with around 30 experts during a rigorous review process rivaling the editorial procedure for top-rate scientific journals. In previous years papers selection has been made from up to 130--200 submissions from well over a dozen countries. 10-page extended abstracts of the contributed papers are collected in a volume published by ACM Press and Springer, and are available at the conference. Full versions of a selection of the papers are published annually in a special issue of the Journal of Computational Biology devoted to the RECOMB Conference. A further point in the program is a lively poster session. From 120-300 posters have been presented each year at RECOMB 2000. One of the highlights of each RECOMB conference is a collection of nine keynotes awarded to researchers of highest international esteem who are asked to inform the community about landmark advances in computational and experimental research and inject new directions into the field of computational molecular biology. This includes the following conference events: Next we present a list of the names of the students and postdocs supported. Those supported either presented a paper (10 in 2001, 6 in 2002, 7 in 2003, 14 in 2004, and 20 in 2006) or were they presenter of a poster. This support was vital to the quality and success of the Conference. At the conclusion we give the publication details of the relevant Recomb proceedings

Time-delayed models of gene regulatory networks

We discuss different mathematical models of gene regulatory networks as relevant to the onset and development of cancer. After discussion of alternativemodelling approaches, we use a paradigmatic two-gene network to focus on the role played by time delays in the dynamics of gene regulatory networks. We contrast the dynamics of the reduced model arising in the limit of fast mRNA dynamics with that of the full model. The review concludes with the discussion of some open problems

Bulletin of Mathematical Biology - facts, figures and comparisons

The Society for Mathematical Biology (SMB) owns the Bulletin of Mathematical Biology (BMB). This is an international journal devoted to the interface of mathematics and biology. At the 2003 SMB annual meeting in Dundee the Society asked the editor of the BMB to produce an analysis of impact factor, subject matter of papers, submission rates etc. Other members of the society were interested in the handling times of articles and wanted comparisons with other (appropriate) journals. In this article we present a brief history of the journal and report on how the journal impact factor has grown substantially in the last few years. We also present an analysis of subject areas of published papers over the past two years. We finally present data on times from receipt of paper to acceptance, acceptance to print (and to online publication) and compare these data with some other journals

Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention

Metallochaperones regulate intracellular copper levels.

Copper (Cu) is an important enzyme co-factor that is also extremely toxic at high intracellular concentrations, making active efflux mechanisms essential for preventing Cu accumulation. Here, we have investigated the mechanistic role of metallochaperones in regulating Cu efflux. We have constructed a computational model of Cu trafficking and efflux based on systems analysis of the Cu stress response of Halobacterium salinarum. We have validated several model predictions via assays of transcriptional dynamics and intracellular Cu levels, discovering a completely novel function for metallochaperones. We demonstrate that in addition to trafficking Cu ions, metallochaperones also function as buffers to modulate the transcriptional responsiveness and efficacy of Cu efflux. This buffering function of metallochaperones ultimately sets the upper limit for intracellular Cu levels and provides a mechanistic explanation for previously observed Cu metallochaperone mutation phenotypes

Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex

Nuclear Pore Complexes (NPCs) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells, but its transport mechanism is still not understood. The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides, known as FG nucleoporins, lining its passageway. Their conformations and collective dynamics during transport are difficult to assess in vivo. In vitro investigations provide partially conflicting results, lending support to different models of transport, which invoke various conformational transitions of the FG nucleoporins induced by the cargo-carrying transport proteins. We show that the spatial organization of FG nucleoporin assemblies with the transport proteins can be understood within a first principles biophysical model with a minimal number of key physical variables, such as the average protein interaction strengths and spatial densities. These results address some of the outstanding controversies and suggest how molecularly divergent NPCs in different species can perform essentially the same function

Spatiotemporal establishment of dense bacterial colonies growing on hard agar.

The physical interactions of growing bacterial cells with each other and with their surroundings significantly affect the structure and dynamics of biofilms. Here a 3D agent-based model is formulated to describe the establishment of simple bacterial colonies expanding by the physical force of their growth. With a single set of parameters, the model captures key dynamical features of colony growth by non-motile, non EPS-producing E. coli cells on hard agar. The model, supported by experiment on colony growth in different types and concentrations of nutrients, suggests that radial colony expansion is not limited by nutrients as commonly believed, but by mechanical forces. Nutrient penetration instead governs vertical colony growth, through thin layers of vertically oriented cells lifting up their ancestors from the bottom. Overall, the model provides a versatile platform to investigate the influences of metabolic and environmental factors on the growth and morphology of bacterial colonies