Job details Print page

The major aim of the CatVis project is to investigate the essential part of the classical visual cycle, the mechanism of all-trans-retinyl ester transformation into 11-cis-retinol carried out by the retinal pigment epithelium 65 kDa protein (RPE65). Whereas genetic disorders that lead to lack of the active RPE65 enzyme causes blindness, controlled inhibition of the protein was recently shown to be promising in macular degeneration treatment. Thus, our multidisciplinary project will focus on two particular mechanistic aspects of the RPE65-dependent step of the visual cycle: the function of the active site and the influence of the protein scaffold. The hypothesis that will be tested in the project is the involvement of an intermediate state that, from a quantum chemical point of view, is a superposition of cationic and radical states.

Our comprehensive approach will include synthesis of the biomimetic models of the RPE65 active site and spectroscopic investigation of its reactivity towards all-trans-retinyl ester augmented with comparative large-scale quantum chemical simulations of the model vs. enzymatic system. The electronic structure of involved species will be investigated with the state-of-the-art table-top X-ray absorption and emission spectroscopy, femtosecond transient absorption spectroscopy, and 2D NMR spectroscopy. The analysis of spectroscopic data will be supported with calculations.

The student involved in the project will carry out quantum chemical calculations that aim to explain the electronic structure changes of the RPE65 active site upon trans to cis isomerization of retinoids.

• investigation of the electronic structure of RPE65 biomimetic models of the active site
• simulations of spectroscopic data
• writing reports and manuscripts’ drafts

• Participation in high impact research;
• Access to modern research linfrastructure;
• Opportunity to work in an interdisciplinary team;
• Participation in international conferences;

• Status of a student in Poland (MSc or PhD studies);
• Specialization in chemistry or physics;
• Experience in quantum chemical calculations;
• Experience in programming;
• Basic knowledge in spectroscopic methods;

• The candidate’s competence to carry out specific tasks in the research project;
• Accomplished projects;
• Research output up to day.