Special event in conjunction with the MILA medical reading group/Événement spécial en collaboration avec le club de lecture en médecine MILA

Fabian Theis

Infos: https://github.com/veugene/medical-reading-group

HIV drug resistance

Thibault Mesplède

In rich settings, HIV drug resistance continues to threaten both public health and the quality of life of individuals. In developing countries, resistance also undermines the efficacy of measures aimed at preventing mother-to-child HIV transmission. The use of modern combinations of drugs helps to limit the emergence of resistance. Resistance develops through the acquisition of specific mutations that impart various defects in viral fitness. Such viral outcomes help to explain the efficacy of specific antiretroviral drug combinations. The future of HIV treatment will rely on two-drug combinations in an unexpected paradigm shift.

Building biology from the bottom-up: synthetic circuits as simple models for gene circuits

Laurent Potvin-Trottier

Engineering synthetic biological systems holds the potential for valuable applications, ranging from environmental remediation to biomedicine. It can also deepen our fundamental understanding of natural phenomena, by building gene circuits and biological systems from the bottom up for example. Synthetic gene circuits are compelling toy models for biological gene circuits, as we know all their components as well as their interactions. These circuits have been engineered to perform a variety of useful tasks, but despite being made from well-characterized biological components, their precision and robustness are usually much lower than their natural counterparts. Our hypothesis for this difference is that synthetic circuits have so far been designed mostly without accounting for the inherent stochastic gene expression in living cells. To demonstrate this, I will show how harnessing principles from stochastic theory to redesign a classic synthetic oscillator (the repressilator, which helped jump-started the field of synthetic biology) helped produce oscillations that rival those of natural clocks. I will then describe how this motivated us to develop a method for screening dynamical phenotypes, by isolating single cells from our microfluidic device using optical tweezers after time-lapse microscopy. This inspired us to engineer hundreds of oscillators to explore areas that are beyond our current theoretical understanding. Finally, I will showcase applications of synthetic circuits to study natural systems, such as measuring bacterial growth in the gut of live mice, and discuss the biological insights learned by engineering precise synthetic circuits.

Single-cell transcriptomic analysis of acute myeloid leukemia and immune checkpoint blockade

François Mercier

Acute myeloid leukemia (AML) is an aggressive cancer of the myeloid lineage of the blood system. Prior work has shown that a rare subset of leukemic stem cells (LSCs) is able to propagate the disease. LSCs are presently only defined functionally as able to engraft by xenotransplantation in immunocompromised mice. No universal markers for LSCs are currently known, therefore previous efforts to study LSCs have relied on enriching for them by cell sorting with non-specific markers. In order to better understand the characteristics essential to LSC self-renewal, we propose to apply single-cell RNA sequencing (scRNA-seq) to study the transcriptional states within human AML samples. While bulk RNA sequencing yields only an average gene expression profile across many cells, scRNA-seq recovers transcripts from thousands of individual cells. This resolution, coupled with the lack of required pre-sorting of cells, provides a less biased view of heterogeneity in cell types and cell states. The overall goal of our research is to exploit scRNA-seq of AML patient samples to study rare leukemic cell populations, such as LSCs and infiltrating immune cells, in order to identify novel, potentially targetable markers.

Les écosystèmes encodés

Frédéric Guichard

Plusieurs propriétés des écosystèmes naturels peuvent expliquer l'émergence de dynamiques complexes dans l'abondance des populations : mécanismes non-linéaires, structure des réseaux trophiques et des réseaux de connectivité spatiale. Il importe aux écologistes de comprendre et d'associer les mécanismes écologiques menant à cette complexité afin de pouvoir déchiffrer les données écologiques, mais aussi afin d'en prédire le rôle pour la stabilité, la diversification et la productivité des écosystèmes en réponse aux perturbation naturelles et anthropiques. à partir de quelques exemples classiques de propriétés écologiques émergentes, je montrerai comment l'interaction entre les interactions écologiques non-linéaires et la structure spatiale des communautés donnent naissance à des dynamiques spatiales caractérisées par une modulation de fréquence et d'amplitude. Cet encodage spontané des signaux écologiques permet leur décodage et ainsi l'inférences des mécanismes sous-jacents. Il procure également aux communautés écologiques une stabilité à une multitude d'échelles spatiales. Ces propriétés ont des conséquences importantes pour l'analyse des séries temporelles écologiques ainsi que pour leur utilisation en conservation.

Cardiac optogenetics and arrhythmias that can stop themselves

Gil Bub

Cardiac tissue is an excitable system that displays a wide range of spatiotemporal patterns. We use optogenetic methods to control activation patterns in cell culture and whole hearts to generate tractable biological models of cardiac arrhythmias. A particularly promising model combines optogenetics with real-time control to generate reentrant circuits. These experiments provide new insights into why some arrhythmias persist and others spontaneously stop on their own.

Silent cancer agents: the ecology and evolution of oncoviruses

Carmen Lia Murall

Globally, 1 in 10 cancers is caused by a virus. Yet the vast majority of oncovirus infections do not progress to cancer or mortality. It is unclear, why these viruses, even with their potent oncogenes, are not more virulent. Under what conditions do they drive cancer? As we develop vaccines and treatments against oncoviruses, we create novel selective pressures and environments for which these oncoviruses can evolve. I will present my work into general oncovirus oncogenicity and I will discuss advancements in our understanding of the ecology and evolution of human papillomaviruses. Papillomaviruses are the best understood family of human oncoviruses and the global use of multi-strain vaccines against them is allowing us to study vaccine-driven evolution potential in human populations.

Martin Sauvageau

Erica Moodie