PhD (M/F) Biophysics: Multiscale modelling of electric transmembrane potential to understand and fight cancer development

Job Description

Thesis Subject

The transmembrane resting potential (TMRP) is a fundamental characteristic shared by all cells, and is an essential ingredient of cell behaviour. It emerges from a difference in electric potentials between intra- and extracellular spaces and is a signature of the cell. The TMRP is finely controlled by the cell through gates (ion channels, IC) allowing the exchange of charges with its microenvironment. A specific type of IC, gap junctions (GJ), enable the exchange of charges between neighbouring cells, transforming living tissues into bioelectric networks. Such networks play a critical role, serving as an organizing principle to maintain tissue homeostasis. While resilient, such networks can be dysregulated by exogeneous perturbations, creating an imbalance across the network, jeopardizing tissue organization.
In particular, the role of TMRP in the development of cancer is increasingly being stressed. TMRP distribution has indeed a major influence in tissue patterning. Dysregulation of TMRP can therefore break tissue structure, leading to a chaotic cellular organization, which is one of the first step of carcinogenesis. Importantly, cancer cells are associated with a lower TMRP compared to healthy cells, which is associated with proliferative behaviour. Dysregulation in IC expressions also promote migratory and metastatic behaviours. Finally, direct effects of the tumour microenvironment (contact microenvironment, hypoxia, interstitial pressure) also participate to the dysregulation of bioelectric signalling.
On the other hand, TMRP can be modulated using external electric field offering promising treatment avenues. This scattered line of evidence shows that the dysregulation of cell bioelectric activity spans multiple scales, with emergent multicellular behaviour, and includes complex couplings with the cell microenvironment. This makes it challenging to create an overarching experimental rationale that captures the extent of the role played by bioelectric signaling in cancer initiation, promotion, and progression.
The goal of the PhD project is then to bridge this gap, and build an interdisciplinary framework with at its core a multiscale model, derived using porous media methodologies, informed via dedicated experiments on 2D and 3D cell culture, that considers bioelectric signalling as a dynamic network. This new representation will enable the description of TMRP distribution in a tissue as a process emerging from collective cell activity, capturing multiscale effects while including local couplings with the cell's microenvironment. The project can be broken into three goals: 1) understanding the role of bioelectric networks in maintaining tissue homeostasis 2) predicting the consequences of their dysregulation in carcinogenesis 3) exploring their modulation during the application of external electric fields (in particular electroporation), using liver cancer as a proof-of-concept. The PhD program will then include both the development of the model and the associated cell culture to inform and validate it.
In this context, the ideal candidate will have a background in biophysics, bioengineering, or mechanical engineering with a very strong drive to work at the interface with life science, as they will receive training in cell culture, fluorescence microscopy and application of electric field. Experience in modelling the impact of electric field with living systems (electroporation) is appreciated.

Your Work Environment

IPBS:
The IPBS (CNRS/UT) hosts more than 250 scientific and administrative staff, including more than 60 PhD students and postdoctoral fellows of multiple nationalities, who work in a stimulating and highly collaborative environment. The IPBS currently comprises 18 research groups working in two broad research areas: the biology of tissue and cellular microenvironments, and the molecular and structural mechanisms of disease. Four facilities provide state-of-the-art technology in proteomics, biophysics and structural biology, molecular and cellular imaging, and functional exploration. The institute is located on Toulouse University Paul Sabatier Campus and is well connected to the city with metro, bus and cable car accessible within 5 minutes walk
Cellular biophysics group
The Cellular Biophysics Group is a pioneer in exploring the interactions between electric fields and living systems. Their work spans the development of electroporation-based treatments and technologies (such as electrochemotherapy and electrogenetherapy) as well as the study of bioelectric processes underlying cancer progression and tissue regeneration. By integrating multiscale approaches—from in silico models to in vitro (2D and 3D) and in vivo systems—the group fosters a highly interdisciplinary research environment to advance both fundamental and applied bioelectricity research.
Perks of CNRS
• Minimum salary of 2300€ per month
• 44 days PTO
• Remote work possible (up to 2 days a week)
• Up to 75% of commute cost (public transportation) covered and sustainable mobility plan (up to 300€)

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

The research professions