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Offer for Ph.D. position (closed)

Structural and parametric identification of bacterial regulatory networks


Description

Recent advances in molecular biology and in biophysics have led to new technologies for measuring cellular processes at the molecular level and in real time. These techniques include gene reporter systems, fluorescence and luminescence microscopy, microfluidics and mass-spectrometry measurement of metabolites. The new sources of data that are thus becoming available provide a wealth of information for the quantification of the interactions in the regulatory networks governing the cellular processes, such as the adaptation of the physiology of bacteria to the environment. Data are especially promising for addressing what is commonly considered as a bottleneck in cellular regulatory network modelling, i.e. the simultaneous identification of structure and parameters (connectivity and regulation logics) of the networks.

The objective of the thesis is the development of methods for the structural and parametric identification of regulatory networks that fully exploit the data sources mentioned above. The project will be carried out within the team IBIS of INRIA Grenoble - Rhône-Alpes. Depending on the interests of the candidate and on the priorities encountered, the project will focus on several among the following methodological issues :

-  The choice of appropriate modeling formalisms. A special attention will be devoted to models combining discrete properties (Boolean functions) and continuous dynamics (ordinary and piecewise linear differential equations, stochastic differential equations, ...) ;
-  The study of model identifiability in the presence of noisy data, different time scales and hidden variables ;
-  The design of maximally informative experiments for identification, for instance by the use of information-theoretic approaches ;
-  The development of effective algorithms for the parametric and structural identification of the system, based on the chosen modelling formalism.

These problems will be addressed by the aid of experimental data and models available within IBIS or via the participation of IBIS to national and international projects. The thesis will focus in particular on the regulatory networks involved in the adaptation of the enterobacterium Escherichia coli to changes in the environmental carbon sources. These networks are investigared by J.Geiselmann (member of IBIS) at the Microorganism Pathogeny and Adaptation Laboratory of the Université Joseph Fourier.

Skills and Profile

Candidates should have a background in mathematics, computer science or physics, preferably with a specialization in system identification or control theory. Programming skills are necessary and knowledge of scientific software (Matlab, Scilab, Maple, Mathematica,...) is desirable. A strong interest for biological applications is essential. Successful candidates will be working in an international and multidisciplinary environment.

Environment

This position is offered at the INRIA Grenoble - Rhône-Alpes Research Unit of INRIA, located near Grenoble and Lyon. The Unit includes more than 600 people, within 34 research teams and 10 support services.

Application and further information

The project is funded by the Rhône-Alpes region. The duration is 3 years. Monthly salary will be around 1900-2000 euros (gross).

Interested candidates should contact :

Eugenio Cinquemani

Hidde de Jong