Missions

Buruli ulcer is a necrotic skin infection of mycobacterial origin that was first reported clinically in 1948 by Australian researchers. Classified as a neglected tropical disease by the World Health Organisation, this infection caused by Mycobacterium ulcerans affects several thousand patients per year, 90% of whom live on the African continent. Buruli ulcer combines major tissue necrosis, local analgesia and defective inflammation, which is particularly unusual from a biological point of view. It was discovered in 1999 that M. ulcerans secretes an exotoxin called mycolactone A/B which is responsible for all the biological effects observed in Buruli ulcer. This major discovery triggered intense efforts to synthesise mycolactone and to understand how this molecule can mediate these effects. Our efforts in this area have led to the establishment of several mycolactone synthesis pathways and we have been associated with the discovery of several biological targets in collaboration with laboratories in France and abroad (see for example : Itskanov, S.; Wang, L.; Junne, T.; Sherriff, R.; Xiao, L.; Blanchard, N.; Shi, W. Q.; Forsyth, C.; Hoepfner, D.; Spiess, M.; et al. A common mechanism of Sec61 translocon inhibition by small molecules. bioRxiv 2022, 2022.2008.2011.503542. DOI: 10.1101/2022.08.11.503542). Among the many questions opened by this work, we are currently interested in the synthesis of new simplified analogues of mycolactones and in studying their effects on one type of target. The synthesis part will be conducted in the team and the proteomic studies, in which the post-doc will be involved, will be carried out at the Institut Pasteur in Paris.

Activités

The candidate will be responsible for the chemical synthesis of mycolactone analogues and their characterization. He/she will participate in the definition of the synthesis routes, documenting the different approaches and his/her own results. He/she will participate in all discussions with the collaborators of the Institut Pasteur in Paris. He/she will write a final report of his/her work and participate in the writing of the different articles (discussion and experimental part) resulting from this work. The candidate will be integrated in a team and will participate in the collective tasks of the laboratory as well as in the different seminars and conferences.

Compétences

We are looking for a candidate with a PhD in organic chemistry and good theoretical and practical knowledge of organic chemistry, good written and oral communication skills and organisational abilities. The candidate will have an interest in the chemistry of natural products and their applications in life sciences. The Laboratory and the team welcome students of all levels from France and from several continents; the candidate should therefore have a team spirit and an interest in working with colleagues from other horizons. Good command of the English language (written and spoken) at B2 level according to the Common European Framework of Reference for Languages.

Contexte de travail

The candidate will join the Biomolecules, Synthesis and Methods (BSM) team of the Laboratory for Molecular Innovation and Applications (LIMA - UMR CNRS 7042, lima.unistra.fr) in Mulhouse and will work under the supervision of Dr. Nicolas Blanchard. Our research themes are the development of original synthesis methods and new reaction concepts with applications in natural products chemistry, life sciences or materials science. LIMA is the largest laboratory dedicated to molecular chemistry research in Alsace and its objectives are to develop new innovative synthesis methods, to validate therapeutic strategies and to apply them in fields such as bioorganic and pharmaceutical chemistry, eco-responsible chemistry and materials chemistry. For more information on our team: http://bsm.unistra.fr/

Informations complémentaires

Please submit a full CV, a summary of your research activities and the email addresses of at least two referees who can be contacted.