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ARD 2020 - Biopharmaceuticals
(Open to international experienced researchers)
ResearchTitle: Bioproduction of bioactive molecules by yeast metabolic engineering
Research Field: Molecular Biology
The region Centre-Val de Loire Ambition for Research and Development 2020 (ARD 2020) Biopharmaceuticals Programme is supported by LE STUDIUM Loire Valley Institute for Advanced Studies for the attraction and recruitment of international experienced researchers and scientific animation.
The Biopharmaceuticals Programme aims to further develop and strengthen the region Centre-Val de Loire biopharmaceutical industries by capitalising on the recognised capabilities of the multidisciplinary research teams from the regional research institutions.
The ARD 2020 Biopharmaceuticals Programme focuses on the design and biosynthesis of molecules for preclinical and clinical development by including the search for synergies with conventional chemically synthesized drugs. The programme involves working with a wide spectrum of molecules (vaccines, therapeutic antibodies, nucleic acids...) with the need for a diverse range of competences and the involvement of teams with complementary expertise. The researchers present in the region Centre-Val de Loire, working in the disciplines of life sciences, are invited to participate and work in synergy, for inter-sectorial development and innovation, in the pharmacy/health sectors to deliver socio-economic outcomes.
The successful candidate will be invited for a one-year fellowship and will benefit from the dynamic scientific environment of the region Centre-Val de Loire (France).and will be part of an outward looking and stimulating pluri-disciplinary scientific and international community.
Nowadays, around 60% of drugs from the human pharmacopoeia contain molecules synthesized on the basis of plant model compounds or directly extracted from plants. This makes of plant sourcing a main concern in the context of global warning and reduction of arable land areas while active molecule demand constantly increases. As such, ensuring a continuous supplying becomes awkward without endangering natural resources. In contrast to plant harvesting, biotechnical approaches based on metabolic engineering strategies offer sustainable solutions to provide alternative sources of pharmaceutically interesting compounds. In this context, the EA2106 “Plant Biocompounds and Biotechnology” (BBV) research team from University of Tours focuses on the elucidation of the biosynthetic pathways of plant specialized metabolisms and their engineering through biotechnologies.
One of the main current research projects of the BBV laboratory relies on the heterologous bioproduction in yeast of the anticancer drug precursors (vindoline and catharanthine that correspond to monoterpene indole alkaloids or MIAs) originally synthesized in the Madagascar periwinkle. More specifically, it involves 1) the characterization of each gene encoding the enzymes from these biosynthetic pathways,
2) their transfer into yeast to reconstitute parts or entire biosynthetic pathways and
3) the culture of the resulting yeast in bioreactors to ensure the synthesis of the expected compounds. BBV is internationally recognized for its expertise in biosynthetic pathway elucidation and has developed a specific set of molecular tools for studying the Apocynaceae plant family.
BBV also possesses strong skills in culturing plant and yeast cells in bioreactors and has a guaranteed access to the bioproduction facilities of University of Tours to ensure the scale up of the production. However, up to now, BBV expertise in yeast molecular engineering mostly relies on conventional transformation approaches allowing protein expression through stable gene integration into the genome or via auto-replicative plasmids.
The successful candidate will help to fill this gap and deploy the latest molecular tools to construct yeast engineered strains efficiently producing the anticancer MIAs.
The research scientist will use state-of-the-art concepts and tools in molecular yeast engineering to create yeast strains synthesizing high amounts of vindoline and catharanthine. Besides optimizing gene coding sequences and their environnement, determining the best integration sites, gene copy number, the succesful researcher will also reconfigure yeast primary metabolism to ensure enzyme cofactor supplying. Optimization of the synthetic fluxes and limits of hijacking syntheses will also be carried out through modulating balance of gene expression level by using coordinated promoter strengh controlling each transfered gene.
The research scientist will integrate an active research team (around 40 members) including plant/yeast molecular biologists, biochemists, plant physiologists/biotechnologists, specialist of process engineering and hosting several foreigner researchers (https://twitter.com/bbvea2106, https://fr-fr.facebook.com/BBVEA2106/) . She/he will work on an ambititous project supported by the Region Centre-Val de Loire (ARD2020 Biopharmaceuticals programme) in close collaboration with an industrial partner and in direct relation with an European H2020 project. She/he will also benefit from expertise and equipement from ther BBV lab (all molecular biology devices, cell imagning, bioreactors, UPLC-MS/MS...) and from the state of art facilities of the University of Tours. His/her relocation and integration will be supported by LE STUDIUM Loire Valley Institute for Advanced Studies.
The fellowship is intended to attract an experienced international researcher in possession of a doctoral degree and a minimum of five years of full-time research experience, preferably ten.
The position is based in Tours, France and offers a contract of one year.
The successful candidate will be welcomed into the ARD 2020 Biopharmaceuticals Programme network and LE STUDIUM faculty of international research fellows working in the region Centre-Val de Loire. She/he will be provided with the necessary means of work (laboratory facilities, office, phone, internet access, access to databases, computer tools, etc ...).
The scientific working languages are French and English.
Entitlements detailed in the French labour contract of employment include:
The deadline for application is 31st January, 2019.
Position is expected to be filled in the 2Q2019.
The application shall consist of three elements:
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