The Pasteur Museum is housed in the apartment where Louis Pasteur spent his final seven years and offers a rare behind-the-scenes look at the living and working environment of the world-renowned scientist. Visitors can gain a unique insight into his everyday life alongside his wife and can admire his rich and diverse scientific work.
The Institut Pasteur’s scientific strategy focuses on developing original and innovative topics and promoting interdisciplinary and multidisciplinary cooperation and approaches. The Institut Pasteur teams have access to the technological resources needed to speed up and further improve the quality of their outstanding research.
Ever since the introduction of the world’s first "Technical Microbiology" course in 1889, teaching has been a priority for the Institut Pasteur. The Institut Pasteur has an international reputation for quality teaching that attracts students from all over the world who come to further their training or top up their degree programs.
With international courses, PhD and postdoctoral traineeship, each institute of the Institut Pasteur International Network (RIIP) contributes to the transmission of knowledge with the training of young researchers all around the world. In this context, doctoral and postdoctoral programmes, study and traineeship fellowships are available to scientists. Alongside training, dynamism and attractiveness of RIIP will result in the creation of 4-year group for the young researchers.
The absence of classical transcriptional regulation through cis-acting sequence elements and transacting factors in Leishmania and the largely constitutive expression at both transcript and protein levels raise the question on how these parasites regulate the developmental transition between insect-stage promastigotes and vertebrate-stage amastigotes, and how they can evolve intra-species divergence in drug susceptibility, tropism, and infectivity as documented in numerous epidemiological field studies.
We scientifically address these questions by (i) investigating parasite-specific molecular mechanisms that govern Leishmania environmental adaptation using systems-wide analyses, and (ii) applying functional genetic approaches on underlying molecular players to reveal their biological relevance in parasite viability and infectivity.
We then translate our basic research findings on Leishmania-specific biology into preclinical applications through drug target validation and anti-leishmanial compound screens. Today, this scientific strategy to develop and apply innovative approaches to gain insight into parasite-specific biological processes relevant for therapy and disease prevention is at the core of two major research axes (Fig. 1).
The first axis is focused on the analysis of Leishmania signal transduction pathways that are relevant for adaptive parasite differentiation in the mammalian host and that qualify as novel targets for anti-parasitic drug development. We established and applied a series of genetics and phosphoproteomics approaches that provided important new insight into (i) the regulation of the Leishmania stress response at post-translational level, (ii) the role of chaperone expression and phosphorylation in parasite viability and infectivity, and (iii) the structure, function, and regulation of various Leishmania protein kinases.
The second axis investigates parasite-specific mechanisms of Leishmania genome plasticity and its consequences for parasite phenotypic variability.
Applying systems-wide approaches at protein, transcript, and gene levels allowed us (i) to link parasite environmental adaptation to genetic copy number variation implicating both amplifications and deletions at the chromosome and gene levels, and (ii) to reveal a mechanism of gene dosage compensation by epigenetic silencing through cis-regulatory long non-coding RNAs (lncRNAs). This peculiar Leishmania feature of genome plasticity bears direct relevance to the phenotypic variability observed in Leishmania field isolates with respect to drug susceptibility, pathogenicity, and tissue tropism, and will be at the core of a new translational effort in bio-marker discovery.
Figure 1: The two major basic research axes of the ParSig Unit and their translational potential.