Biomedical Honours students who completed their laboratory-based project with Dr William Fuller in the School of Medicine are the first three authors in his newest publication available today in the Journal of Biological Chemistry. The research provides understanding on the process of heart muscle relaxation between beats which may lead to new targets for treating heart disease. Fiona Plain, Rachel Yee and Samitha (Dilini) Congreve were honours students with Dr Fuller in 14/15, 15/16 and 16/17 respectively.
Dr Fuller said, “I have always been impressed with the intellect, energy and drive of the final year honours students that I have supervised. So, I always look to get the best out of them, and give them the opportunity to contribute to the research programmes in my laboratory, as well as educating them during their projects. These three accomplished students did magnificently to get a great deal out of three challenging projects, and have a lot to be proud of. It is really satisfying for me to be able to put them in an environment where they can fluorish, and watch them realise the full extent of their talent. Furthermore, the paper has been selected as Editor’s pick for this edition of the journal, which means they consider it to be amongst the top content they receive each year.”
The heart is a pump that contracts and relaxes rhythmically from birth to grave. Relaxation is achieved simultaneously in all the cells of the heart as a result of the removal of calcium ions from these cells. This allows the heart to refill with blood ready for the next beat. Work in Dr Fuller’s lab has discovered a new way in which this process of calcium ion removal is controlled in the cells of the heart: palmitoylation. Palmitoylation is a chemical change made to certain proteins that changes the way they work and where they go in the cell. One of the main routes for calcium to leave the cell, a protein called NCX1, is palmitoylated. This is important because when NCX1 goes wrong this leads to heart disease.
In the current study, the team led by Dr Fuller, focused on this particular protein. By deleting regions of NCX1, they worked out that a small region of this protein contained the ‘instructions’ that cells recognise in order to carry out the palmitoylation reaction. If they changed the sequence of the ‘instructions’ then the cell no longer understood them and NCX1 was not palmitoylated anymore. Most elegantly, if they attached these ‘instructions’ to a protein that should not usually be palmitoylated, then cells would read the instructions and perform the palmitoylation reaction on that protein. This represents a fundamental advance in the understanding of an important cellular process.
“It’s very exciting to have our research selected as an Editors pick in JBC. It’s great to see work largely carried over three different honours projects making it to publication, and is testament to the excellent research and training happening within the Fuller lab,” said first author Fiona Plain. Fiona graduated from Dundee in 2015 and won the Sir James Black Award for outstanding contribution to research and scholarship in her field. She has continued working in Dr Fuller’s laboratory as a British Heart Foundation (BHF) funded PhD student.
Rachel Yee who graduated in 2016, received a highly commended in The Undergraduate Awards 2016 for her entry based on a summary of her honours project, which included work published in this study. This commendation was achieved in the face of considerable competition: 5,514 submissions from 243 universities in 40 countries! Rachel said “My honours project experience has been very enriching and has greatly expanded my scientific capabilities. Furthermore, working in a wonderful lab environment like Dr. Fuller's has certainly expedited that process! I am glad that all the hard work has finally culminated in a published paper, and which will hopefully lead to further advancements in cardiac biology research.”
Samitha Congreve who graduated this month was nominated this year for the Sir James Black Award. She is a recipient of the Ali Knox Undergraduate Award, awarded to a student who, in the opinion of their fellow students and staff, has demonstrated determination and enthusiasm in overcoming enormous obstacles to succeed in their studies, and will soon start a PhD funded by a prestigious BHF PhD Fellowship in Dr Fuller’s lab. When asked about her experience, Samitha said "My Honours project was one of the most enriching experiences during my studies as an undergraduate. It is truly rewarding that our hard work is being recognised and contributing to the advancement of this field of research. It has inspired me to further expand my knowledge in cardiovascular research as I pursue my post-graduate studies. I would like to thank Dr. Fuller and his lab for this wonderful experience."
Building on this important discovery, Dr Will Fuller and Professor Mike Ashford in the Division of Molecular & Clinical Medicine in the School have been awarded a Special Project Grant of £637,445 from the BHF to will support the continuing investigation into the role of NCX1 palmitoylation in both normal cardiac function and the development of heart disease. “NCX is essential for all sorts of processes in the cardiovascular system, and is known to go wrong in certain diseases. This research will make a fundamental difference to our understanding of how NCX works, and may uncover new treatment targets in heart disease,” explained Dr Fuller.
‘An Amphipathic α-Helix Directs Palmitoylation of the Large Intracellular Loop of the Sodium/Calcium Exchanger’ is available to read now in Journal of Biological Chemistry.
Photo (left - right): Fiona Plain, Rachel Yee and Samitha (Dilini) Congreve