Doctoral Fellowship in Philosophy of Developmental Biology

The UCLouvain ARC (Actions de recherche concertées) project Epistemodevo is hiring a funded PhD fellow in the philosophy of biology (more precisely, the philosophy of developmental biology). The fellowship will last four years, and will involve the candidate working with me as supervisor, as well as being embedded in the labs of three practicing developmental biologists: René Rezsohazy, Françoise Gofflot, and Frédéric Lemaigre.

We are thus seeking a PhD candidate in philosophy of science who has at least some experience with or training in molecular biology, with a serious interest in working in an interdisciplinary team situated between the philosophy of biology and biological practice.

• Application deadline: Rolling; candidates will be evaluated until a selection is made. To have your application evaluated for the first selection period, submit by May 31, 2023.
• Starting date: Negotiable, between September, 2023 and September, 2024
• Duration: Four-year PhD fellowship
• Required skills: Training in philosophy of science and philosophy of biology; interest in working in an interdisciplinary environment; familiarity with or training in molecular biology
• Other advantages: Familiarity with STS or sociology-of-science approaches could be beneficial for working closely with scientific colleagues, but is not required
• Language: While the university as a whole is French-speaking, all four lab groups involved in the project use English as their working language. It is expected that the doctoral dissertation would be written in English. Knowledge of English is thus essential; knowledge of French (or desire to learn) could be beneficial socially.

The Project

The abstract of the overall project, including the work packages to be performed by the groups in developmental biology, is:

Following the capacity to modify genes in animal genomes, developmental biology has flourished as a discipline predominantly aiming at understanding how genes and gene regulatory networks (GRNs) shape tissues, organs and organisms. Several biologists and philosophers have, however, criticized the dominance of this gene-centric view of life which tends to overemphasize the search for and intervention on genes. In that context, the teams of F. Gofflot (FG), F. Lemaigre (FL) and R. Rezsohazy (RR) have already investigated how transcription factors (TFs) integrated in GRNs control developmental processes. In line with standard practice in the field, their conclusions were often formulated using idealized GRNs as models representing the genetic control of development. We now propose to approach developmental processes by adding an additional layer of regulation after gene transcription and translation (or “hypogenetic” regulation) and to address the epistemological implications of this change in viewpoint.

At the experimental level, we will characterize a neglected layer of molecular regulations taking place at the level of proteins, namely TF stability, which is potentially a key determinant of developmental regulators’ function. Specifically, we will focus on Homeobox A1 (HOXA1), HOXA5, and Hepatocyte Nuclear Factor 6 (HNF6). These three TFs share features that make them suitable for comparative studies: they are key regulators of cell fate determination and bind to target DNA via a conserved homeodomain. Their roles have been well documented by inactivation or over-expression approaches. In contrast, their modes of action have been neglected. Our goal is thus to characterize the longevity of these TFs, to determine the protein domains, interactors and molecular pathways controlling their stability, and to evaluate how modulating TFs’ stability impacts developmental processes like heart development (HOXA1), synaptogenesis in the brainstem (HOXA5) and hepatic cell differentiation (HNF6). We thereby intend to integrate protein stability as an underestimated determinant of GRN function. Further, together with the team of C.H. Pence (CP), philosopher of biology, the epistemological dimension of our project will evaluate the importance of and changes in practices of model building and idealization in describing complex developmental processes. In particular, we will explore the extent to which adding this extra layer of protein regulation changes the theoretical and experimental presuppositions of the proposed biological work, investigating whether the whole is, potentially, more than the sum of its parts. In our project, philosophers and biologists will work together in the labs to invest philosophy in practice and to question the way hypotheses and conclusions are drawn by experimentalists when proposing biological models and theories.

Your Contribution

As you can see, in short, the biological advances here propose to move beyond the traditional gene regulatory network (GRN) framework for understanding gene regulation in developmental biology. The empirical work of the three biological labs involved in the project will attempt to add to a GRN picture an understanding of what happens to the relevant proteins after translation. The philosophical project, then, is to evaluate the epistemic consequences of this empirical move.

While I will work with the candidate to help refine the particular project in line with their interests, some general possibilities for the dissertation topic could include:

• What does this empirical work tell us about the nature of idealization in developmental biology? It’s widely recognized that GRNs are an idealization, but what does the process of removing those idealizations look like? The philosophical literature on idealizations largely focuses on the preservation of idealizations rather than their elimination, making this potentially an exciting case study.
• How does the process of model construction work in biological practice? What can we learn about the choices that our biological colleagues make while designing experiments and moving into a relatively uncharted area like this one? How does knowledge about the protein-stability concerns investigated by the biology groups relate to other kinds of projects to construct alternative models in developmental biology?
• What is the role and nature of causal inference in these complex, multi-scale network models of regulation? How should we evaluate the relative quality of those inferences, and how does the experimental design work in the everyday practice of these three biological labs relate to the ways in which we might theorize about them?

Eligibility Criteria

Note that you will need to have finished a research (120h) master’s degree (or equivalent) in order to be considered eligible to enter UCLouvain’s doctoral programs. It is possible that an exception could be made for a candidate coming from North America who does not hold a master’s degree (i.e., who would normally get one in the process of getting a doctorate, as is common in the United States); if you are interested in the position and in this situation, please send me an email and we can discuss things further.

Your master’s degree must also be in philosophy or a closely related field. Unfortunately, entrance requirements make it nearly impossible for a student trained only in biology to enter the philosophy Ph.D. program here.

Selection Process

Candidates are asked to prepare the following materials:

• Short cover letter expressing interest and motivation (maximum 1 page)
• Curriculum vita
• Sample of written work (maximum 30 pages)
• List of courses and grades from the master’s degree, as well as the grade from the master’s thesis and any report from the thesis defense (if available)
• The names and email addresses of two professors whom I could contact for a reference, if needed

Candidates are requested to e-mail all documents to me directly at charles@charlespence.net.

Additional Comments

For more information on life as a doctoral student in the lab, please visit the lab’s web page: https://pencelab.be/people/doctorate/.

For more information about the project, please do not hesitate to email me: charles@charlespence.net