Biotrack

Systems biology analysis of autoimmune diseases

REF: PD 05
Principle investigator:
Pablo Villoslada
Contact details:

pvilloslada(ELIMINAR)@clinic.ub.es

RESEARCH LINE NO LONGER AVAILABLE

Research framework

We want to understand the pathogenesis of autoimmune diseases such as Multiple Sclerosis (MS) by analyzing the signalling networks controlling the immune response. More specifically, we plan to built models of cytokine and T cell receptor signalling pathways based in previous knowledge and from in vitro assays using primary cells (CD3+, monocytes) from patients with MS and controls stimulated with pathway specific stimulus and inhibitors and assessing pathway activation by detecting phosphorylation of key molecules (xMAP assays). Models will be built using ordinary differential equations (ODE) and boolean networks and analyzed using network theory and dynamic analysis.

The most common techniques that will be used are: Experimental in vitro assays and xMAP will be performed by technicians. The postdoc must be expert in bioinformatics and systems biology being confident in using R or Matlab software and being familiar with ODE and networks model analysis.

The most relevant publications that support the research made are:

  • Vandenbroeck K, Comabella M, Tolosa E, Goertsches R, Brassat D, Hintzen R, Infante-Duarte C, Favorov A, Escorza S, Palacios R, Oksenberg JR, Villoslada P. United Europeans for development of pharmacogenomics in multiple sclerosis network.
  • Pharmacogenomics. 2009 May;10(5):885-94.
  • Villoslada P, Steinman L, Baranzini SE. Systems biology and its application to the understanding of neurological diseases. Ann Neurol. 2009 Feb;65(2):124-39.
  • Tegnér JN, Compte A, Auffray C, An G, Cedersund G, Clermont G, Gutkin B, Oltvai ZN, Stephan KE, Thomas R, Villoslada P. Computational disease modeling -fact or fiction? BMC Syst Biol. 2009 Jun 4;3:56.
  • Vélez de Mendizábal N, Carneiro J, Solé RV, Goñi J, Bragard J, Martinez-Forero I, Martinez-Pasamar S, Sepulcre J, Torrealdea J, Bagnato F, Garcia-Ojalvo J, Villoslada P. Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis. BMC Syst Biol. 2011 Jul 15;5:114. PubMed PMID: 21762505.
  • Villoslada P, Baranzini S. Data integration and systems biology approaches for biomarker discovery: Challenges and opportunities for multiple sclerosis. J Neuroimmunol. 2012 Jan 24. [Epub ahead of print] PubMed PMID: 22281286.

We have developed new approaches based in systems biology to the understanding of the pathogenesis of MS. As such we have described that protein networks of the differentially expressed genes in autoimmune diseases have specific characteristics such as connecting modules (high betweenes). Moreover, we have developed a mathematical model of the regulation of T cells that explain the oscillatory behaviour of autoimmune diseases and provide the basis for linking the activity of the immune system with the course of the disease. At present we are focusing in the study of type I interferon pathway and the TCR because both have been associated with the pathogenesis of MS and the response to current immunotherapies.

Our team has pioneered the application of systems biology to autoimmune diseases and MS in particular. Based in the previous developments we have made, we are better positioned to apply systems biology models for improving the understanding of the disease. Also, we are in the path of using this approach for developing new biomarkers of MS that would be useful at the clinical level in the near future.

Keywords

Systems biology, bhioinformatics, signalling networks, autoimmunity, multiple sclerosis

Main Challenges

We are interested in a scientist that have achieved some accomplishments in bioinformatics or systems biology by having contributed with proceedings to mathematics or physics meetings (as this is the common way of communication for these disciplines) as well as having published in top journals on the field.

The candidate will interact with scientist from different disciplines (mathematicians, physicists, biologists, physicians). Skills searching for information in databases, learning new algorithms and implementing - adapting previous mathematical models to new projects are required.

The researchers should interact with young scientists and technicians (training-teaching and providing guidance) in order to integrate in the research program. This person should extend collaborations and the prestige of our team/center in the field of systems biology applied to medicine

We are looking for a scientist with a background in bioinformatics, mathematics or physics, but with knowledge in biology and expertise in having addressed biological problems. We are interested in a scientist knowledgeable in network theory and/or systems dynamics or mathematical modelling of biological process. As such, in addition of a PhD in bioinformatics/systems biology, we would appreciate extended experience in the analysis of medical problems of different kind (genomics, biochemistry, cell biology).

Team strategic objective in IDIBAPS

Apply our discoveries to the clinical management of patients with multiple sclerosis. We pursuit such by applying systems biology, imaging or neurobiology technologies to the challenged posed by MS.

As the coordinating team of the RETICS REEM (Spanish Multiple Sclerosis Network - www.reem. es) we aim to transverse diffusion of knowledge and optimum use of synergies, with a view to transferring the advances in research to the clinical practice setting and to patients.

Lastly, the group has a constant commitment to innovation trying to cover the gap in financing existing between basic research and the clinical phase development of new drugs on the part of the biopharmaceutical industry.

(Read eligibility criteria)