The OXYTRAIN training network (see www.oxytrain.eu) offers 12 PhD fellowships for a program on mechanistic and applied enzymology research. OXYTRAIN is a joint academic/non-academic training initiative supporting the convergence of biochemistry, enzyme engineering and biotechnology.
The most talented and motivated students will be selected for a 3-year advanced multidisciplinary research training, starting July 2017. Fellows will obtain specialist training through cutting-edge research projects, specialist advanced courses and training schools, complemented by workshops on transferable skills. In addition, fellows will have the opportunity to go abroad on international secondments at leading places in academia and industry.
The OXYTRAIN research program aims at developing effective oxygenases that can be used for selective oxidation reactions. This project, ESR2, will focus on improving the rate of catalysis, understanding the molecular basis for formation and stabilisation of the oxidising enzyme intermediate in Flavin Monooxygenases (FMO) and boosting enzyme robustness by establishing (1) efficient _expression_ systems for soluble and membrane-bound eukaryotic FMOs; (2) protocols for protein purification as to provide the material for structural and biochemical studies; and, (3) providing structure determination of enzymes and enzyme-ligand complexes including analysis of valuable mutants.
The work will involve the production, crystallization and structure elucidation of human FMOs, as no structure is available yet for these flavoproteins, in spite of them playing a crucial role in metabolism of drugs and metabolites. The FMOs will also be studied regarding their mechanistic features.
The Structural Enzymology group, headed by Prof Mattevi, is currently hosting five Postdoctoral Fellows, five PhD students, a technician and several Master students. The common theme of the research projects in the group is the investigation of medically relevant proteins and enzymes with interesting chemical properties. The core of the research activity is represented by X-ray crystallography, employed to study protein three-dimensional structures; this is complemented by other approaches such as biochemistry, biophysics, cell biology and computational chemistry. Key contributions include the first crystal structure of a Baeyer-Villiger monooxygenase (phenylacetone monooxygenase from Thermobifida fusca), the first crystal structure of a thermostable Baeyer-Villiger monooxygenase (Cyclohexanone monooxygenase from Thermocrispum municipale) and the first crystal structure of a Baeyer-Villiger monooxygenase active on large cyclic ketones (polycyclic ketone monooxygenase from Thermothelomyces thermophile). On the study of FMOs, the group has recently published the characterization of human isoform 5 (FMO5) revealing the atypical in vitro activity of it as a Baeyer–Villiger monooxygenase on a broad range of substrates, revealing the first example to date of a human protein catalysing such reactions; previously, the group provided the x-ray structure of a soluble prokaryotic FMO from Methylophaga sp. strain SK1, the protein of known structure with the highest sequence similarity to human FMOs.
For more information on ESR2, please visit http://www.oxytrain.eu/esr2/
For more information on the 12 individual research projects, please visit www.oxytrain.eu/phd-vacancies/
Start and duration of the PhD positions
Who can apply?
How to apply?
After 20th March 2017 we will select 20-24 candidates who will be invited to attend the recruitment days, 18 & 19 April 2017 in Amsterdam.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska Curie grant agreement No. 722390.
J Rubén Gómez Castellanos, DPhil