PhD position - Structural basis of melanogenesis enzymes

Context & Job description

Project title: Structural basis and molecular mechanisms of human tyrosinase enzymes in melanogenesis

Melanin is a natural pigment crucial for photoprotection against UV radiation. In humans, melanin biosynthesis involves a multistage chemical process performed by enzymes called tyrosinases. Mutations tyrosinases cause albinism, with reduced production of melanin in skin, hair and eyes. Despite their pivotal roles in melanogenesis, the catalytic mechanism and the substrate specificity of human tyrosinases are largely unknown. This thesis project aims to unveil the melanin biosynthesis pathway, in particular, the catalytic mechanism of tyrosinases. In partnership with ImmuSmol, you will focus on the profiling of tyrosinase metabolites and their pathway activites in melanocytes. Furthermore, you will, using  X-ray crystallography in the Structural Biology Group at the ESRF, determine the 3D structures of tyrosinases in complex with relevant metabolites. The outcome of this project will enable (1) the identification of specific pathway metabolites and (2) the elucidation of tyrosinase metabolite-binding and catalytic activity at the atomic level. Taken together, this work will shed light on the molecular basis of melanogenesis and will be key for the analysis and design of efficient compounds to treat melanogenic diseases and pigmentation disorders.

Further information may be obtained from Montserrat Soler-Lopez (email: solerlop@esrf.fr)

Expected profile

  • Degree allowing enrollment for a PhD (such as MSc, Master 2 de Recherche, Laurea or equivalent) in biology, biochemistry or closely related science.
  • A background in molecular biology and protein biochemistry is essential, knowledge of macromolecular crystallography would be an advantage.
  • Proficiency in English (proof of upper-intermediate level must be included in the application.. Applicants  originating  from  native-English-speaking  countries  can  apply  without  the  need  for  proof  of level. An official degree conducted in English will be also accepted as a proof).
  • Compliance with the Marie Sklodowska-Curie mobility rule: candidates may not have resided or carried out their main activity (work, studies, etc.) in France for more than twelve months in the three years immediately before the date of recruitment.
  • At the date of recruitment, early-stage researchers must be in the first four years of their research careers and have not been awarded a doctoral degree.
  • Candidates must satisfy the conditions for enrollment in a doctoral programme

More details about the application procedure can be found at  www.innovaxn.eu/for-students/documents/

Working conditions

The successful candidate will be enrolled in the doctoral school of Chemistry and Life Sciences of the University of Grenoble and will be based, other than a 3-month secondment at the biotech company ImmuSmol (Bordeaux, France), at the ESRF (Grenoble, France). In addition to tuition in the skills required of the PhD research project, a varied training programme in soft skills and other areas will be offered to the successful candidate throughout the 3-year PhD project.

More details on the InnovaXN programme can be found at www.innovaxn.eu

Company description

InnovaXN is a Horizon 2020 MSCA COFUND programme providing an opportunity for 40 industrial companies to work with 40 PhD students, performing advanced research and exploiting the unique techniques available at the ESRF and ILL. As collaborations with industry and  innovation are the central themes of the programme, InnovaXN will provide a unique cross academic-industry science setting, secondment opportunities and society-relevant research, training future key researchers to tackle major research and societal challenges.

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