Institute of Physical Chemistry PAS, Team 20 “Cooperative catalysis”
National Science Centre of Poland
Project title, type and project number
Combined experimental and theoretical studies of the catalytic activity of RPE65 enzyme using biomimetic active centre models (CatVis) 2020/39/B/ST4/01952, 50/2023
Project leader
Dr hab. Adam Kubas
Description
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.
Number of vacancies
1
Key responsibilities include
Position in the project
Scholarship
Job type
Student – scholarship position
Salary
2 000 PLN per month
Position starts on
1.12.2023
Maximum planned period of contract/stipend agreement
12 months with the possibility of extension
We offer
Link to Euraxess website
see websiteMore details
see websiteScientific profile of a candidate
First Stage Researcher (R1)
Requirements
Key assessment criteria
Planned interviews: around 20.11.2023 (the recruitment committee reserves the right to conduct an interview with selected candidates, about which they will be informed separately)
How to Apply: Send application directly to rekrutacja@ichf.edu.pl; IMPORTANT! email subject: "Recruitment no. 50/2023"
Application deadline
16.11.2023 16:00
Deadline for the settlement of the competition
27.11.2023
Archival announcement. We would like to thank all candidates for their submitted applications.