PhD Research Project: From Molecules to Vision; Identifying molecular mechanisms that mediate opsin
Photoreceptors of the vertebrate eye are exquisite biological sensors capable of detecting single photons. Light sensitivity of photoreceptors is mediated by hundreds of millions of opsin molecules tightly packed into hundreds of membrane folds that form the so-called outer segment.
As the outer segment is constantly renewed throughout the lifetime of the organism, it is estimated that 100-1000 opsin molecules are transported to the outer segment every second. The molecular mechanism that mediates opsin transport is one of the central unsolved puzzles of photoreceptor biology. This transport mechanism is also of paramount medical importance as its defects lead to photoreceptor death and blindness in a range of human genetic disorders, including retinitis pigmentosa, cone-rod dystrophies, Bardet-Biedl Syndrome and others.
The goal of this project is to identify molecular mechanisms that mediate opsin transport. This will be accomplished using biochemical and imaging approaches. Biochemistry experiments will include tandem affinity purification (TAP), a two-step protocol designed to recover intact protein complexes from cells and tissues. In parallel, transport mechanism components will be localized at high resolution using advanced imaging super-resolution microscopy techniques, stochastic optical reconstruction microscopy (STORM) in particular.
The Malicki lab has long experience with studies of the visual system in general and photoreceptor cells in particular. For details of our past contributions to this and other fields, please visit https://www.sheffield.ac.uk/bms/research/malicki .
This project is funded by Fight For Sight, an eye research charity. Funding includes a stipend of 17,000 GBP/year for three years and a travel allowance. It also pays Home/EU fees for three years. Overseas students are welcome to apply but would need to supplement the difference in the Home/EU fee and the overseas fee.
Applicants are expected to have excellent record of academic performance, and research experience in biochemistry and molecular genetics. Interested individuals are encouraged to contact Dr. Jarema Malicki for further details. Review of applications is in progress.