. .

Frontiers of Life Science PhDs

“Frontières du Vivant” (FdV)

projects involve interactions between a broad range of academic disciplines, in the pursuit of understanding living systems. Students who join the doctoral school are trained in various disciplines (e.g. biology, physics, medicine, economy, linguistics) from around the world.

Degree requirements

The PhD at the FdV program represents a combination of research experience gained in the hosting lab and experience in interdisciplinary science-related activities gained through the doctoral school. Students are required to complete the FdV training program, which consists of at least 300 hours of training. Half of the hours must be completed through FdV approved courses, workshops, or activities and the remainder may be completed through external programs, international conferences, summer schools, etc.

The doctoral school does not require a determined number of publications to authorize the defense. However, it recommends that students are involved in 3 publications during their thesis:

  • One research article written with the lab, not necessarily as lead author, and not necessarily on the student’s main subject.
  • One review type article, taking advantage of the work of interdisciplinary synthesis expected by the school.
  • One research article as lead author on the student’s main subject.

Approval to defend the thesis is granted by the doctoral school director. The director will consider the following: the Thesis Advisory Committee recommendations, research achievements, publications or dissemination of the work in thesis, and completion of the doctoral school training program including courses, conferences, and involvement in the FdV doctoral program.

Featured Life Science projects

Randomness and variability in animal embryogenesis, a multi-scale approach

The developmental polarity and morphogenesis of a single cell

Unraveling the neural circuitry of sequence-based navigation using a combined fos imaging and computational approach

Mechanotransductional regulation of mesoderm invagination and posterior endoderm invagination of the Drosophila embryo

Symmetry breaking and Cell polarization imposed by an external mechanical cue

 Featured Frontiers of Life Science Projects

Traditionally, students have pursued interdisciplinary research projects in natural sciences, engineering and technology, medical and health sciences. Recently, projects in the life sciences have incorporated approaches and/or applications from other disciplines including the social sciences and humanities, however the focus of the work is on advancement of knowledge in life science.

The following featured dissertations received the highest honors from their defense committees: Mention Très honorable avec Félications

This grade is reserved for candidates with exceptional skills proven by their achievements and the quality of their thesis defense. It can be awarded only if a) there is a unanimous agreement of the thesis jury members under an anonymous vote and b) the jury president writes and signs an additional report justifying this distinction.

Paul Villoutreix, PhD
Former FdV Student
Graduated July 2015

Randomness and variability in animal embryogenesis, a multi-scale approach

We propose in this thesis to characterize variability quantitatively at various scales during embryogenesis. We use a combination of mathematical models and experimental results

In the first part, we use a small cohort of digital sea urchin embryos to construct a prototypical representation of the cell lineage, which relates individual cell features with embryo-level dynamics. This multi-level data-driven probabilistic model relies on symmetries of the embryo and known cell types, which provide a generic coarse-grained level of observation for distributions of individual cell features. The prototype is defined as the centroid of the cohort in the corresponding statistical manifold. Among several results, we show that intra-individual variability is involved in the reproducibility of the developmental process.

In the second part, we consider the mechanisms sources of variability during development and their relations to evolution. Building on experimental results showing variable phenotypic expression and incomplete penetrance in a zebrafish mutant line, we propose a clarification of the various levels of biological variability using a formal analogy with quantum mechanics mathematical framework. Surprisingly, we find a formal analogy between quantum entanglement and Mendel’s idealized scheme of inheritance.

In the third part, we study biological organization and its relations to developmental paths. By adapting the tools of algebraic topology, we compute invariants of the network of cellular contacts extracted from confocal microscopy images of epithelia from different species and genetic backgrounds. In particular, we show the influence of individual histories on the spatial distribution of cells in epithelial tissues.

Daria Bonazzi, PhD
Former FdV Student
Graduated March 2015

The developmental polarity and morphogenesis of a single cell

How cells establish their proper shapes and organization is a fundamental biological problem. In this thesis, I investigated the dynamic development of cellular form and polarity in the rod-shape fission yeast cell. These studies are based on monitoring how small symmetric fission yeast spores grow and self-organize to break symmetry for the definition of their very first polarity axis.

In a first part, I studied interplays between surface mechanics of the spore cell wall and the stability of Cdc42-based polarity domains which control spatio-temporal aspects of spore symmetry breaking. In a second part, I studied mechanisms by which these polarity domains control their width and adapt it to cell surface geometry, a process likely relevant to understand how functional cortical domains scale to cell size.

Overall these novel investigations focusing on how cells dynamically develop their form and polarity de novo highlight complex feedbacks in morphogenesis that cannot be evidenced by looking at cells at “steady state” or with genetics.

Bénédicte Babayan, PhD
Former FdV Student
Graduated June 2014

Unraveling the neural circuitry of sequence-based navigation using a combined fos imaging and computational approach

Spatial navigation is a complex function requiring the combination of external and self-motion cues to build a coherent representation of the external world and drive optimal behaviour directed towards a goal. This multimodal integration suggests that a large network of cortical and subcortical structures interacts with the hippocampus, a key structure in navigation.

I have studied navigation in mice through this global approach and have focused on one particular type of navigation, which consists in remembering a sequence of turns, named sequence-based navigation or sequential egocentric strategy. This navigation specifically relies on the temporal organization of movements at spatially distinct choice points. We first showed that sequence-based navigation learning required the hippocampus and the dorsomedial striatum. Our aim was to identify the functional network underlying sequence-based navigation using Fos imaging and computational approaches. The functional networks dynamically changed across early and late learning stages.

The early stage network was dominated by a highly inter-connected cortico-striatal cluster. The hippocampus was activated alongside structures known to be involved in self-motion processing (cerebellar cortices), in mental representation of space manipulations (retrosplenial, parietal, entorhinal cortices) and in goal-directed path planning (prefrontal-basal ganglia loop). The late stage was characterized by the emergence of correlated activity between the hippocampus, the cerebellum and the cortico-striatal structures.

Conjointly, we explored whether path integration, model-based or model-free reinforcement learning algorithms could explain mice’s learning dynamics. Only the model-free system, as long as a retrospective memory component was added to it, was able to reproduce both the group learning dynamics and the individual variability observed in the mice.

These results suggest that a unique model-free reinforcement learning algorithm was sufficient to learn sequence-based navigation and that the multiple structures this learning required adapted their functional interactions across learning.

Benjamin Driquez, FdV
Former FdV Student
Graduated October 2013

Mechanotransductional regulation of mesoderm invagination and posterior endoderm invagination of the Drosophila embryo

During Drosophila gastrulation, two waves of constriction occur in the apical ventral cells, leading to mesoderm invagination. The first constriction wave is a stochastic process mediated by the constriction of 40% of randomly positioned mesodermal cells and is controlled by the transcription factor Snail.

The second constriction wave immediately follows and involves the other 60% of the mesodermal cells. The second wave is controlled by the transcription factor Twist and requires the secreted protein Fog. It is known that Snail mutation lead to the loss of the two constriction phases but a mechanical poking on the mesoderm cells can rescue de second phase of Twist dependent constriction.

The interactions between the two constriction phases, la secreted protein Fog and the molecular motor Myosin II with a numerical simulation. The posterior endoderm invagination that presents similarities with mesoderm invagination have been study, as well as the interaction between them.

Finally with an other numerical simulation, the hypothesis of an induced invagination on a primitive mechanosensible organism ( the HAECKEL grastrae ) on the contact with the oceanic floor has been tested.

Philippe Bun
Philippe Bun, PhD
Former FdV Student
Graduated October 2013

Symmetry breaking and Cell polarization imposed by an external mechanical cue

Cell polarity establishment implies a symmetry-breaking event, resulting in an axis along which the cell reorganizes. Studies on morphogenesis and cytokinesis reveal the implication of the cortical actomyosin contractility in cell shape changes. Whether the initial event that triggers polarity arises spontaneously or requires an external cue remains controversial.

Here we show that single and weak integrin-mediated mechanical cue applied on detached round fibroblasts is required to control the location and duration of symmetry breaking of cortical actomyosin gel instability. Furthermore, we demonstrate that cells respond at a macroscopic level since the induced asymmetric actomyosin flow triggers the 3D migratory polarization axis and determines its orientation.

As an initial event, the microtubule-independent actomyosin flow polarizes towards the opposite pole of the cue and drives higher contractility at the rear of the cell that persists after the application of mechanical stress has been halted. Microtubules are further required for long-term growth of leading edge protrusion associated with the MTOC reorientation relative to the cue.

These findings support a model whereby the stochastic and transient symmetry breaking events occurring in detached oscillating cells are not able to drive cell polarity establishment, the mechanical stress being required to trigger processes of global auto organization required for long-term functional polarization.

The symmetry breaking bias mechanism revealed here in single cells likely emerges as a relevant mechanism for other key processes occurring in tissue morphogenesis.

Read about more PhD projects from our current students and alumni.