Magali CASANOVA

HDR – PHD

Past experience

After defending my PhD thesis in 2008, I became a lecturer at Aix-Marseille University in 2009, teaching at the Faculty of Pharmacy. From my PhD to 2019, I worked on the protozoan parasite Leishmania. The latter is responsible for leishmaniases, which are neglected tropical diseases from the World Health Organization priority research program. I notably focused on Leishmania cell death and autophagy, bringing me experience in molecular and cellular biology of the parasite. In 2019, I have defended my HDR. After 4 years in a lab working on Mycobacterium, I joined the LAI in September 2023.

Current projects

I am working on Leishmania, which are protozoan parasites responsible for leishmaniases, considered as neglected tropical diseases by the World Health Organization priority research program. Present in 88 countries on 5 continents, these vector-born diseases are responsible for around 30,000 deaths a year, with an annual incidence of 700,000 to 1 million new cases. Leishmaniases are transmitted by the bite of a female sandfly. More precisely, inside the insect digestive tract, Leishmania cells are in an elongated flagellated form. Once they have been injected into the mammalian host, Leishmania cells are in a round form with a very reduced flagellum called the amastigote form, inside phagocytic cells, notably macrophages. For the moment, no human vaccine exists, as well as no prophylaxis, vector control is difficult, and there is no satisfactory treatment for these diseases, due to the cost, side-effects and mode of administration of current drugs, but also to the development of drug resistance. In this context, I am developing two research areas, in collaboration with the ‘Centre National de Référence’ on leishmaniases in Montpellier.

Consequences of global warming on Leishmania cells

As neglected tropical diseases, leishmaniases are rife in poor tropical countries. However, these diseases are also a problem in other countries, like in Europe and North America. This is not only due to human and pet movements. Indeed, in westernized countries, leishmaniases are a major problem in immunocompromised people, whereas the number of such people is increasing. Furthermore, the increase of the number of Leishmania strains resistant to the usual drugs is becoming a problem. Last, the temperature increase due to global warming is inducing a significant increase in the number of leishmaniases. More precisely, the temperature increase would induce an increase in the survival, and the mobility of sandflies, as well as an increase in their population density and the number of sandfly bites. However, these current studies focus on the consequences of global warming on sandflies, whereas quite no study concerns the pathogen itself. Yet, the promastigote forms are subjected to the same temperature variations as the insect. Thus, I am interested in the consequences of temperature increase on Leishmania parasites: notably, are the growth, the cell cycle, the motility, or the virulence of the parasite affected? I am studying these features on different Leishmania species and with different temperature conditions (increase during a few hours, or during several days). For this, I am using the facilities in the LAI: cell culture platform, cytometry, microscopy, biophysics tools to study cell motility, … This research area is based on a ‘one health’ approach.

Study of Leishmania apoptosis

Leishmania parasites have a very original organization in comparison to higher eukaryotes. For example, despite a classic pattern of apoptosis, key mammalian apoptotic proteins are not present in Leishmania, such as caspases, cell death receptors and anti-apoptotic molecules. Even if some features have been described on this very original apoptosis, a lot of things have to be done to better understand it. This would allow a better understanding of the organization of living beings and of the eukaryote evolution. This would also allow the identification of new therapeutic tools based on Leishmania apoptosis, thus new, specific and so non-cytotoxic treatments. For this, I am notably trying to identify proteins and molecules involved in Leishmania apoptosis, to describe the different apoptotic pathways in Leishmania, and to encapsulate key proteins or DNA to induce Leishmania apoptosis.

Affiliation

Aix-Marseille University