Ongoing projects
Receptor internalization
Growth factor receptors are rapidly internalized after binding to their ligand. In physiological conditions, this internalization is mostly driven by clathrin-mediated endocytosis. Receptor ubiquitylation plays a central role in this process, directing internalized receptors towards the degradative lysosomal compartment. In contrast, non-ubiquitylated receptors are recycled back to the cell surface. Regulation of the whole process has a major impact on intracellular receptor signalling. The ubiquitin ligase Itch has been involved in this process through its ability to interact with SH3 domain-containing proteins that play a major role in clathrin-mediated endocytosis. We are investigating the role of Itch in receptor internalization and the mechanisms through which it regulates endocytosis and signalling.
Mitochondrial-derived peptides
Animal's mitochondrial genomes (mtDNA) code for only 13 proteins, all involved in the Ox/Phos pathway. Most of these coding sequences, 12 out of 13 in humans, are located on the same string of the mtDNA. It is generally thought that both strands of the mtDNA are entirely transcribed from two central promoters, with the functional transcripts produced from these precursors by RNases. However, this model needs to be reevaluated in light of recently discovered small peptides derived from mammal mtDNA. In silico analysis of the mammalian mitochondrial genome reveals about 250 putative additional peptides that could be produced in the organelle. The identification and characterization of peptides effectively produced in mitochondria will no doubt help to improve our knowledge and understanding of the mitochondrial transcription and translation mechanisms. This project is conducted in collaboration with the The Breton Lab.
Mitophagy
In animals, mitochondria are inherited strictly through the mother lineage, the spermatozoid mitochondria being rapidly targeted to mitophagosomes for degradation soon after fecundation. A notable exception to this rule is found in several species of bivalve molluscs, where male mitochondria are conserved into the male germ cell line, partially escaping mitophagy. Although the general mechanism through which this phenomenon occurs is unknown, specific male and female open reading frames have been found in the male and female mitochondrial genomes. These sequences have been shown to be expressed in the mitochondria of a few species. By examining and characterizing these proteins, we should be able to determine their involvement in this process and eventually shed light on this curious evolution. This project is conducted in collaboration with the The Breton Lab.
Development of molluscan cell lines
To this day, no attempt at producing a permanent molluscan cell line has been successful. Although the technical challenges are many, the discovery of bivalve neoplasia fitting tumour criteria is a strong indicator that the development of such cell lines is feasible. Such a tool would be precious for our projects in comparative cell physiology and to many other laboratories. The first steps are to optimize primary cell culture conditions and suitable transfection methods and expression vectors. From there, heterogenous expression of oncogene will allow the development of immortalized cell lines, suitable for long-term cell culture projects.