PhD on conceptual approaches to cancer (Univ. Bordeaux, France)

PhD at the University of Bordeaux, France

Supervisor: Thomas Pradeu (Research Director at CNRS, PI Conceptual Biology & Medicine Team, ImmunoConcept, CNRS & Univ. Bordeaux)

Start date: October 1st, 2021. Duration: 3 years.

Application deadline: April 1, 2021.

Funding: SIRIC-Brio and Region Nouvelle Aquitaine

Open to: scientists and MDs interested in conceptual approaches to cancer and philosophers interested in daily and intensive interactions with biologists and/or MDs.

Cancer raises fascinating questions from a triple point of view: experimental, medical, and conceptual. This project focuses on the conceptual aspects, while proposing a strong experimental dimension.

The central idea is to think about cancer in terms of evolution, by proposing a comparative approach, taking as a starting point the question of when cancer appeared in evolution and in which species cancers can be found today. More specifically, we propose to think of cancer as a deregulation of the essential mechanisms that ensure multicellularity, and to explore some important consequences of this definition.

This question can be explored in two distinct experimental projects. The student will choose the project they prefer. (Other options are possible: see below).

Option 1: Multicellularity and cancer in yeast

Scientific co-supervisor: Bertrand Daignan-Fornier (Research Director at CNRS, IBGC)

Partner lab: Institute of Cellular Biochemistry and Genetics (IBGC, UMR5095)

Project description: This experimental evolution project will consist in inducing the evolution of multicellularity and then the evolution of cancer in yeast, a normally unicellular organism. The snowflake-type yeast experimental model is already in place in the host lab (IBGC). The first task will be to determine the conditions for the emergence and maintenance of multicellularity in yeast, including the appearance of essential properties of multicellularity such as the division of labor between distinct cell types. Indeed, division of labor and differentiation are generally accepted as key steps of “true multicellularity”. These properties have been described in the scientific literature on “major evolutionary transitions”, but rarely reproduced and tested experimentally. On this basis, we will try to determine which perturbations of the characteristics of multicellularity lead to cancer or what we call “quasi-cancer”. Thus, the goal will be to create multicellularity and then cancer in an organism in which these two phenomena do not usually exist, in order to better understand the conditions of cancer emergence and, if possible, to formulate new hypotheses on the mechanisms of cancer resistance in mammals and, ultimately, in humans.

Keywords: Cancer; multicellularity; experimental evolution; yeast.

Option 2: Immune system, cancer and multicellularity

Scientific co-supervisor: Vanja Sisirak (CNRS Research Fellow, ImmunoConcept)

Lab: Immunoconcept (UMR5164)

Project description: It is now well established that the immune system influences the growth and spread of cancer. The immune system can inhibit this process but also, more paradoxically, promote it. The goal of this PhD project is to understand the links between the immune system and multicellularity. We will ask whether the immune system can be conceived as a “guardian” of multicellularity, what role the immune system plays in the development and dissemination of cancers across different species, and whether the appearance of a cancer reflects a dysfunction in immune surveillance. From an experimental viewpoint, the work will consist of a comparison between a classical model, the mouse, and a non-classical model, the mole rat, a rodent of particular interest because it almost never develops cancer. Firstly, we propose to examine the consequences on the immunity of mice of a perturbation of certain properties central to multicellularity, such as cell adhesion, proliferation or division of labor. This question can be addressed in vitro and using organoid models, before being explored in vivo in mice. Secondly, virtually nothing is currently known about the immune system of the mole rat, so we propose to test the hypothesis that the mole rat’s immune system plays a role in the anti-cancer mechanisms of this organism. Finally, the objective will be to use the mole rat as a model that can generate new and experimentally testable hypotheses on the control of cancer in mice and possibly, ultimately, in humans.

Keywords: Cancer; multicellularity; immunity; immunoediting.

The priority target audiences for this PhD are students trained in biology or medicine with a strong interest in conceptual issues. Students with a background in Cancer, Genetics, or Immunology-Microbiology are particularly encouraged to apply. Students with a background in Philosophy of biology and/or medicine are also welcome to apply, provided that they are willing to work in close collaboration with scientists.

Whatever the chosen option, the candidate will propose, in agreement with the PhD supervisor and the rest of the laboratory, a division of his/her working time between the conceptual and experimental dimensions, knowing that the conceptual dimension cannot be less than 30%. The PhD supervisor will be Thomas Pradeu (Research Director at the CNRS at the ImmunoConcept lab), the lab of affiliation will be ImmunoConcept (UMR5164) and the team of affiliation will be the “Conceptual Biology and Medicine” team, co-directed by Maël Lemoine and Thomas Pradeu.

Although a clear priority will be given to the two possible topics described above, any proposal for a topic related to cancer, featuring an innovative conceptual or theoretical approach, and based on tight interactions with scientists, may be considered.

How to apply?

– Either to ask a question or to apply, please send an email to Thomas Pradeu.

– Material:

– CV

– Motivation letter (3 pages maximum; please explain why you are interested in conceptual approaches to cancer and why you are interested in joining our interdisciplinary team; if your background is in philosophy, please explain why you want to work in close collaboration with scientists and/or MDs)

– One example of your previous work that you particularly like (paper,  chapter, etc.)

– Two letters of recommendation (to be sent directly to Thomas Pradeu).

Some recent and relevant publications of the team:

– Pradeu T. (2019), Philosophy of Immunology, Cambridge University Press.

– Rondeau E., Larmonier N., Pradeu T. and Bikfalvi A. [co-senior authors] (2019) Philosophy of biology: Characterizing causality in cancer eLIFE 8:e53755.

– Laplane L., Duluc D., Bikfalvi A, Larmonier N., and Pradeu T. (2019), Beyond the tumour microenvironment. International Journal of Cancer 145(10), 2611-2618.

– Pradeu T. (2019), Philosophy of Biology: Immunology and individuality, eLIFE 8:e47384.

– Laplane L., Mantovani P., Adolphs R., Chang H., Mantovani A., McFall-Ngai M., Rovelli C., Sober E., and Pradeu T. (2019), Why science needs philosophy. Proceedings of the National Academy of the Sciences USA (PNAS) 116 (10) 3948-3952.

– Laplane L., Duluc D., Larmonier N., Pradeu T. & Bikfalvi A. [co-senior authors] (2018), The Multiple Layers of the Tumor Environment. Trends in Cancer 4(12), 802-809.

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