PhD position H/F on synthetic organic chemistry and protein chemical synthesis

Updated: 7 months ago
Location: Tremblay en France, LE DE FRANCE
Deadline: 15 Jul 2019

The PhD work will be performed within the CBF team, which belongs to the research unit UMR CNRS 8204, located in Lille at the Pasteur Institute of Lille (France).
The CBF team has a recognized expertise in protein chemical synthesis by developing novel chemical tools for building chemoselectively proteins from unprotected peptide segments in water.
The CBF team in Lille is also one of the rare teams in the world maintaining the whole Sm life-cycle. Therefore, the scientific environment provided by the CBF team is strongly interdisciplinary.
The project involves a collaboration with LIEC team (Université de Lorraine, Metz, France).Quantifying the antifreeze properties of D-AFPs (thermal hysteresis) requires the rare expertise of LIEC team who will host and train the PhD student to this specific technique.
The best AFPs will be tested for the cryopreservation of invertebrate models in Lille for Sm and Metz for Gm (PhD will ensure the exchange of expertise between Lille and Metz).

Schistosoma mansoni (Sm) is one of the five worm species responsible for schistosomiasis, a disease that affects 260 million people in the word and cause 200 000 deaths per year. Sm has a complex life-cycle that involves two hosts, a fresh water snail and a mammalian host (humans, hamsters in the lab). Schistosomiasis tends to spread and starts being observed in some developed countries such as in Corsica. Developing new drugs against Sm is an important goal and requires to maintain its life-cycle in the laboratory, which can never be stopped since the only cryopreservative technique developed so far (on schistosomules) is poorly reproducible and leads to massive worm death (> 95%). The cryopreservation of Sm larval stages would constitute a breakthrough by permiting to stop temporarily the life-cycle, by reducing the costs and number of hamsters used to maintain the life-cycle, by facilitating the storage or the exchange of strains and by simplifying the organization of compound screening and anti-parasitic drug development. The CBF team in Lille is one of the rare teams in the world maintaining the whole Sm life-cycle. Such a cryopreservative approach is also needed for other invertebrates such as Gammarus fossarum (Gm, LIEC team, Metz), a fresh water crustacean employed in ecotoxicology and ecology studies to evaluate the effect of polluants in headwater streams.
This project aims at synthesizing and evolving novel synthetic anti-freeze proteins entirely made of D amino acids (D-AFPs). These proteins will be used for developing innovative cryopreservative techniques for Sm and Gm models. AFPs are known to minimize cryoinjury induced by ice crystal growth in organisms living in cold environments. Used as additives, AFPs should improve the cryopreservation of Sm and Gm models at various stages of their development. By being made of D amino acids, D-AFPs are protease-resistant, non-immunogenic and free of biological contaminants. The D-AFPs can only be produced by chemical synthesis which is the expertise of CBF team. In this environment, the PhD student will use modular chemical approaches for performing structure/activity relationship studies and scale-up. The best AFPs will be selected from a small focused protein library and tested for the cryopreservation of invertebrate models. This innovative and multidisciplinary project gathers a large repertoire of expertise including chemical synthesis, physical chemistry and biology. It will provide a strong interdisciplinary knowledge to the PhD candidate and thus strong assets for its future carrier.

Profile: Master in synthetic organic chemistry, willingness to work at the interface of chemistry and biology
Although not required, an experience in peptide chemistry will be appreciated
Techniques: Synthetic organic chemistry, HPLC, NMR, mass spectrometry, circular dichroism

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