RNA Biology Group and Institute for Cell and Molecular Biosciences Medical School Newcastle University Catherine Cookson Building Framlington Place Newcastle upon Tyne NE2 4HH
Dr Jeremy D Brown
My Bachelor’s Degree is in Pharmacology. My third year final dissertation concerned gene therapy and its potential for treating cancers. I greatly enjoyed writing this dissertation and it sparked a real interest and enthusiasm for the topic. The focus of my PhD is to better understand the mechanism of an unusual event in protein synthesis, in which 2 separated proteins are generated from a single open reading frame. This ‘translational recoding’ is used by a number of viruses as part of the suite of ways in which they generate all the proteins encoded by their genomes. As such it is a potential target for antivirals. In addition, the ability to generate separate proteins from single open reading frames has numerous applications in biotechnology and biomedicine.
Project title: How do viruses trick ribosomes into making two polypeptides from a single open reading frame?
My project considers a unique peptide-driven co-translational recoding event whereby two proteins are produced from a single open reading frame in the absence of a stop and start codon. Both steps of the reaction occur with the ribosome poised at the end of a short amino acid motif, the “2A” peptide, with glycine and proline codons in its active site (the peptidyl transferase centre). My Masters project considered whether this reaction, dubbed the “2A reaction”, could be influenced by changes to ribosomal RNA modifications and/or specific ribosomal proteins. In my PhD project I will continue to examine the 2A reaction, and requirements for it. A key initial step will be to examine the conformation taken by the nascent peptide within the ribosomal exit tunnel. This may lead to efforts to use ribosomes ‘caught in the act’ of the 2A reaction to generate information about and a model of the conformation that the ribosome takes during this unusual translational phenomenon. It will be interesting to uncover more about the 2A reaction as it holds great potential for use in gene therapy and biotechnology. The sequence already has numerous applications but greater understanding would broaden the horizons for use of 2A in research and practice.
I have been involved in an initiative to improve communication of science to younger students called “Leading Edge”. One project required working with six Key Stage 4 students with a 6 month project in the laboratory. Another event involved going to a local secondary school to take part in a week of science designed to inspire and encourage the young students to take an interest in science.
An abstract I have written has been accepted for poster presentation at the North East Post-Graduate Conference.
Where did I get my PIPs
PIPS Internship Organisation Name
When deciding on your internship, what did you want to experience and what did you hope to gain from that experience?
I wanted to experience scientific research in an industrial setting and to see the difference between academia and industry. I also wanted to develop my abilities in the lab, learn new techniques and get involved in an interesting project. I wanted to experience living and working in another country and to see the different culture.
Did you get the experience you were expecting and did you achieve the personal development you had hoped to make?
I got the experience I was expecting from my internship. I worked full time in an industrial laboratory setting. I got a real feel for how the industry worked and what day-to-day life was like. In terms of personal development I feel I achieved a lot; I now have a lot more confidence in my ability and skills, also going abroad was very daunting and I feel that I handled it very well and enjoyed it immensely.
Did you discover anything about yourself or make any achievements that you were not expecting?
I was surprised to find that I actually coped extremely well with being so far away from friends and family and how quickly I settled in to my new surroundings. I discovered that the world is a small place.
Has the internship made you feel differently about potential career options and has it helped to put the skills from research into a broader context?
I think that my internship has opened my eyes a bit to the wide range of possibilities for when I graduate, in the sense that I may never have considered moving abroad before but having seen how amazing it can be I would now consider it. Because my internship was still very much a laboratory based setting I used the skills I possess in much the same way, however, I can see how skills gained from research could be used outside of academia. I think that the internship would be more beneficial in terms of career options at the end stages of the PhD or even after, when the student has fully experienced working for a long period of time in a lab and wants to explore other options.