Claudine CHAOUIYA CHANTEGREL
See web pages of my group Network Modelling
at the Instituto Gulbenkian de Ciência
My research focuses on the modelling and analysis of discrete events systems
, relying on adequate mathematical frameworks. After working on a variety of industrial applications, I made a major change in the 2000s, when I started working on the modelling of biological networks. Since then, my activity has been organised along 3 main lines: methodological work, computational tools and standardisation and concrete biological applications.
- Methodological advances:
With diverse collaborators and members of my groups, we have defined original methods to analyse logical models of regulatory and signalling networks. Because they permit to study much larger models, these methods constitute altogether a significant breakthrough in the field. These advances include:
- Stable states identification and feedback circuit analysis (e.g. DOI)
- Model reduction preserving essential dynamical properties (e.g. DOI)
- Model-checking techniques to verify properties of biological relevance (e.g. DOI)
- Identification and reachability quantification of attractors in asynchronhous logical models (DOI)
- Definition of reverse models to efficiently assess basins of attraction in asynchronous dynamics (manuscript in preparation).
We have also considered the use of Petri nets (PN) in computational biology (e.g. DOI)
- Computational tools and standardisation:
This activity makes the links between methodological developments and concrete modelling studies. Indeed, to make the developed methods available to the community, but also to support our modelling work, we strive to develop appropriate software tools, the most well-known being GINsim, reference tool for the logical modelling of regulatory networks (e.g. DOI).
More recently, my group has developed EpiLog, a new software tool implementing a cellular
automaton framework for the logical modelling of pattern formation on epithelia (DOI).
To ensure reproducibility as well as supporting model exchange,
I was deeply involved in a collective work to set up SBML L3 Qualitative Models package (SBML qual), an SBML package defining a standard format for qualitative
models of biological networks.
We also contributed to the foundation of the Consortium for Logical Modeling and Tools (CoLoMoTo), which brings together modellers, developers of methods and tools, as well as curators.
- Biological case studies: These were performed in collaboration with biologists to develop models of networks controlling a variety of cellular processes, notably:
- Regulatory control of cell adhesion in EMT (in prep)
- Sex determination in different organisms (e.g. DOI)
- Patterns of genetic alterations (co-occurrences and exclusivities) in bladder cancer (DOI)
- Formation of dorsal appendages formation in the fly oocyte (DOI)
- T helper cell differentiation (e.g. DOI)
- Segmentation of the early embryo (DOI)
- Mammalian cell cycle (e.g. DOI)
- CoMEDy (PTDC/BEX-BCB/0772/2014, founded by FCT)
COmputational Modelling platform for Epithelial DYnamics to explore the role of epithelial to mesenchymal transition and stemness acquisition in cancer recurrence.
See the project website for further details.
For most cancers, which stem from epithelial cells, tumour recurrence and metastasis are the major causes of mortality. Recent studies point towards the necessity to take into account intra-tumour heterogeneity to design effective therapies. In particular, a few cells undergo Epithelial to Mesenchymal Transition (EMT), a process by which epithelial cells lose their adhesive properties and are able to migrate. EMT is thus believed to contribute to metastasis. Moreover, the identification of rare populations of tumour initiating cancer cells, Cancer Stem Cells (CSCs), are associated to metastasis and tumour relapse.
While key regulatory pathways defining EMT are mostly known, it has not been clearly established how clonal populations of cancer cells cooperate to drive EMT and to favour the emergence of cells with stemlike features. Besides, the mechanisms explaining the association between EMT induction and the emergence of CSCs have yet to be clarified.
Complex intertwined signalling and transcriptional networks govern cell fate decisions. Moreover, both intra and intercellular processes are at play in the aforementioned cooperation between distinct clonal populations within a tumour, not to mention
influence of the microenvironment, e.g. Extracellular Matrix (ECM). This makes the path from tumour initiation to metastasis exceedingly complex. Computational modelling shows promising avenue to handle this complexity and to improve our
understanding of cancer.
- CANCEL STEM (POCI-01-0145-FEDER-016390, funded by Fundação para a Ciência e a Tecnologia (FCT), through national funds (PIDDAC) and co-financed through the European Regional Development Fund (FEDER)) Tackling cancer stem cells: a challenge and an opportunity to advance in anti-cancer therapy.
This research program, coordinated by Joana Paredes, gathers 18 research teams from 3 top Portuguese institutes (i3s - Porto, CNC.IBILI - Coimbra and IGC - Oeiras). This consortium aims to identify the molecular, cellular and extracellular tumour events that contribute to the acquisition of Cancer Stem Cells (CSC) properties within a neoplastic tissue.
Our group is involved in the project Work Package 3 (CSC plasticity: EMT and stem cell state generation), in collaboration with Carla Oliveira (i3s - Porto).
- MIXED-UP (PTDC/BII-BIO/28216/2017, funded by FCT) Targeting pathogenesis and engineering cell factories: by developing mixed regulatory metabolic genomic models in yeasts.
This project is led my Miguel Teixeira (from IST-ID, Lisbon). The overall goal is to use Systems Biology tools to improve the
therapeutic control of pathogenesis in Candida albicans and C. glabrata, and to improve the productivity
of S. cerevisiae as a cell factory. To do so, genome-scale Boolean transcription regulatory models and
stoichiometric metabolic models will be gathered for the three species, leading to the development of
unified combined regulatory-metabolic genome-scale models for these three species. Based on the use
of these mixed regulatory-metabolic models, this project aims to provide as outcomes promising new
drug-targets and new drugs for the treatment of candidiasis and improved S. cerevisiae cell factories
towards a bio-based economy. Additionally, these platforms, as proof-of-concept, and the methods
created for their development, are expected to have a huge impact in the development of similar
systems biology tools for other organisms.
Our group is responsible for Task 1, Construction of full genome regulatory models for S. cerevisiae, C. albicans and C. glabrata.
- ERGODIC (PTDC/EEI-CTP/2914/2014 founded by FCT) Formal methods for the analysis of modular gEnetic ReGulatOry network DynamiCs.
The project is led by Pedro Monteiro at INESC-ID, Lisbon. Briefly, it aims to develop efficient means based on SAT approaches to analyse the attractors and their basins of attraction in logical models. Our group is involved in Tasks 3, 4 & 5.
CANTROL (PTDC/BBB-BIO/4004/2014, founded by FCT) Deciphering the mechanisms of transcriptional regulation that control antifungal drug resistance in the pathogenic yeast Candida glabrata: aiming the development of improved diagnosis and therapeutic approaches.
This project is led by M. Teixeira at IST-ID, Lisbon. Our group is involved in Task 3, to uncover and anlyse the regulatory networks of S. Cerevisae and Candida glabrata.
- Member of the editorial board of
- BMC Systems Biology (link)
- BMC Bioinformatics (link)
- Scientific Reports (link)
- PLOS One (link)
- SBML Editor
- Coordinator of the ISCB Computational Modeling of Biological Systems (SysMod)