Reader Group - How do protein making factories prevent cardiovascular disease?
- John Reader
ABOUT THE RESEARCH
Ribosomes are fascinating protein-making factories. Ribosomes and the entourage of associated factors are responsible for translating the genetic information encoded within mRNA into amino acid sequences joined together to make proteins. Surprisingly, components of the ribosomal machinery have been recently discovered to have additional roles in eukaryotic cells, including regulation of endothelial cell health. Work from our group has identified a strong genetic link between a ribosomal factor and cardiovascular disease but we do not understand how this works. How do ribosomes regulate endothelial cell health and protection from disease? What is the connection between faulty ribosomes and cardiovascular disease? These are some of the fundamental questions that this project will tackle. Our ultimate goal is to identify novel players in cardiovascular disease and design new therapies that target these pathways.
Additional supervision will be provided by Professor Ellie Tzima and Associate Professor Anuj Noel.
This DPhil will be based at the Reader/Tzima group at the Wellcome Trust Centre for Human Genetics. We are part of a wider scientific community with expertise in cardiovascular biology and the opportunity to be co-mentored and co-supervised by other senior scientists will be made available. The student will have the opportunity to be exposed to a wide range of techniques based on the student’s individual interests. The student will be supervised on a daily basis by a postdoctoral fellow and will be trained in cell culture, siRNA/CRISPR techniques, protein gels and western blotting, ribosomal and polysome profiling, subcellular fractionation, molecular cloning, confocal microscopy, protein structure analysis, and bioinformatics. The student will have the option to conduct animal work, if desired.
Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.
Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.
As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.
The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.
Mehta V, Pang K, Rozbesky D, Nather K, Keen A, Lachowski D, Kong Y, Karia D, Ameismeier M, Huang J, Fang Y, Hernandez A, Reader JS, Jones EY, Tzima E. The Guidance Receptor Plexin D1 moonlights as an endothelial mechanosensor. 2020 Nature 578:290-295
Simpson L, Reader JS and Tzima E. Mechanical regulation of protein translation in the cardiovascular system. Frontiers in Cell and Developmental Biology.2020 8:34
Keen AN, Zhang FR, Reader JS*, Tzima E* Proteostasis and Resilience in the Mechanically-Stressed Vascular Endothelium. Current Opinion in Physiology In Press June 2023
Keen AN, Payne LA, Rice A, Simpson LJ, Del Rio Hernandez A, Reader JS* and Tzima E*. Eukaryotic initiation factor 6 regulates mechanical responses in cells. J Cell Biol. 2022; 222(2):e202005213
(Highlighted in Spotlight: Factoring in the force: a Novel role for eIF6; JCB 2022)