Title: Identification of new players in centriole biogenesis

Supervisor: Mónica Bettencourt-Dias and Mariana Lince-Faria

IGC Group: Cell Cycle Regulation Lab

E-mail: [email protected] 

Abstract:

Centrioles are subcellular structures essential for the formation of cilia and centrosomes, structures existent in the majority of our cells. Misregulation of the biogenesis of these structures is associated with human disorders such as retinal degeneration, infertility, cystic kidney disease and cancer. The molecular mechanisms regulating centriole biogenesis have only recently started to be unravelled, opening new ways to answer a wide range of questions that have fascinated biologists. A hypothesis-driven siRNA screen previously performed by our lab identified a set of new genes involved in centriole biogenesis.

This project aims at the validation of some of the identified candidates. Using different techniques as siRNA mediated gene-knockout in mammalian cells, fluorescence microscopy, Super-resolution microscopy, Expansion microscopy, Western Blot analysis and Drosophila melanogaster genetics, we want to understand the mechanisms of centriole biogenesis regulation as well as its conservation along different species of the eukaryotic kingdom.

Title: Ecology and Evolution in the Gut Microbiome

Supervisors: Isabel Gordo

IGC Group: Evolutionary Biology

E-mail contact: [email protected] 

Abstract: The mammalian gut is home to thousands of species and its diversity is a biomarker of health. In this project we use mice as a model system to understand how dynamic is the gut microbiome and how newly colonisers of the gut evolve. We are interested to discover conditions, such microbe-microbe competition and/or diet supplementation capable of lowering the ability of antibiotic resistant bacteria to persist in the gut. (See Cardoso, Durao, Amicone and Gordo 2020, Nature Ecology & Evolution).

Title: What sets up the asymmetry for early neurogenic divisions in the vertebrate retina?

Supervisor: Caren Norden and Elisa Nerli

IGC Group: Cell Biology of Tissue Morphogenesis

E-mail: [email protected] and [email protected]

Abstract: One fundamental question in developmental biology is how single cells develop into a multicellular organism. Within this process, the generation of cellular diversity is crucial for correct formation and functionality of different organs. The central nervous system is an example in which this diversity is crucial for building neuronal networks and complex functions. To build functional networks, multipotent progenitor cells need to give rise to the correct types of neurons in the proper proportions and with the right timing, while, at the same time, the tissue is still growing. Elucidating these processes requires understanding of how progenitors enter lineage decisions to produce the different neurons at precise timepoints, and how stereotypic these decisions are. 

To contribute to this question, we focus on the quantitative analysis of a neurogenic lineage in the zebrafish retina, the Ath5 lineage. We use live imaging to perform in vivo lineage tracing of Ath5+ progenitors. Within this lineage, we investigate the outcome of two consecutive cell divisions to understand which fate decisions progenitors make, how plastic or stereotypic they are and what regulates them. Overall, this contributes to understanding how progenitors enter the neurogenic path and form the correct types of neurons at the right time.

Two types of projects would be available in this framework to be discussed with potential candidates.

Title: Modifiers of sister chromatid cohesion loss

Supervisor: Raquel Oliveira

IGC Group: Chromosome Dynamics

E-mail: [email protected]

Abstract: Sister chromatid cohesion is essential for faithful mitosis, as premature cohesion loss leads to random chromosome segregation and aneuploidy, resulting in abnormal development. To identify specific conditions capable of restoring defects associated with cohesion loss, we screened for genes whose depletion modulates Drosophila wing development when sister chromatid cohesion is impaired (a first report on the results of this screen can be found here ). This project aims to validate other hits arising from this screen with regard to their ability to modulate defects associated with sister chromatid loss.

Title: Protein complexes by the numbers

Supervisors: Pablo Sartori

IGC Group: Living Physics

E-mail: [email protected]

Abstract: Proteins are the fundamental building blocks of cells. Yet, in order to carry out their function, proteins self assemble into higher order structures referred to as protein complexes. One fundamental difficulty in studying protein complexes is their large diversity. Some complexes, such as microtubules, are polymeric. Others, such as RNA polymerases, grow to well defined size and composition. Some, such as the proteasome, are highly symmetric; whereas others, such as the ribosome, exhibit no symmetries. Similar diversity exists in their kinetics, energetics, composition, etc.

In this project we will quantify the above properties of protein complexes by analyzing publicly available databases, curating literature, and doing back of the envelope estimates. Our goal is to come up with a map of the ensemble of protein complexes, and populate it with few representative examples.

Title: Comparative demography of endangered species using genomic data

Supervisors: Lounès Chikhi, Olivier Mazet and Beatriz Mourato

IGC group: Population and Conservation Genetics (Collaboration with “Institut de Mathématiques de Toulouse”, Toulouse, France)

E-mail contact: [email protected] ([email protected], [email protected])

Abstract: Genomic data have become increasingly available for many taxa including endangered species. In addition, the computational methods used to reconstruct the recent evolutionary history of species from genomic data have become increasingly sophisticated. However, despite the increasing amount of data, most studies focus on one species making it difficult to determine whether the history reconstructed informs us only on that particular species or provides a general information on past changes in habitat or on the influence of human populations on endangered species. Comparative studies are crucially needed but difficult to carry out. In our group we are studying how models of population structure influence the inference of the demographic history of species. In this project the student will analyse in close collaboration with the supervisors the properties of genomic data from species living in the same habitats. We will compare the results of computer simulations and real data from endangered species from the same or neighbouring regions for which genomic data are available. We are thus looking for a candidate who would like to explore with us the properties of past changes in connectivity on genomic data from co-distributed endangered species. The candidate will perform coalescent simulations under varying scenarios (using scripts that have been already developed in the team, she/he will also be able to develop her/his own depending on her/his interests). Simulations will be compared to real data sets from endangered species. More specific details of the project will be discussed with the candidates, as this is an ongoing project.

Title: Testing the confounding impact of sampling schemes and spatial structure on signals of population size change and admixture

Supervisors: Lounès Chikhi and Rémi Tournebize

IGC group: Population and Conservation Genetics

E-mail contact: [email protected] ([email protected])

Abstract: A major interest in population genetics is to reconstruct the demographic history of species using genetic data. Yet, although species evolve in space and time, a large amount of research largely oversees the importance of space. Consequently, several methods used to reconstruct that history assume that population structure, including spatial structure, can be neglected. In other words individuals are analysed as if they were sampled from large populations (often representing continents) wherein individuals reproduce freely without considering spatial distances. By ignoring spatial structure (i.e. the heterogeneous geographic distribution of allele frequencies across a species distribution), these methods can produce results that are interpreted in terms of population size change, admixture or selection when spatial structure might be a contributing factor. Our team is interested in the use of alternative models of species demography that integrate population structure. Previous research suggests that spatial structure can generate signatures that are interpreted as admixture by several commonly used tests or statistics such as the ABBA-BABA test. Still several studies have identified admixture events in lemurs or humans on the basis of this test. In this project the student will carry out spatial simulations in close collaboration with the two supervisors to study the properties of this and other statistics in models with and without admixture. We are thus looking for a candidate who would like to explore with us the properties of spatial processes with applications in endangered species or in the human species. The candidate will perform coalescent simulations under varying scenarios (using scripts that have been already developed in the team, she/he will also be able to develop her/his own depending on her/his interests). Simulations will be compared to real data sets from endangered species or from humans. More specific details of the project will be discussed with the candidates, as this is an ongoing project.