This year’s Tadion Rideal Prize has been awarded to Dr Gerard Pieper from the Randall Centre of Cell & Molecular Biophysics for his doctoral thesis entitled: ESCRT-III/Vps4 controls heterochromatin-nuclear envelope tethering and the establishment of nuclear compartmentalisation through the inner nuclear membrane protein complex Lem2-Nur1.
Gerard’s research was carried out under the supervision of Prof Snezhka Oliferenko and Prof Frank Uhlmann.
On selecting a winner for this year’s award, Dr Nigel Eady, Director of Research Talent for the Centre for Doctoral Studies, who chaired the assessment panel for the award, said:
Gerard Pieper’s research and thesis are extremely impressive. The quality of his work, further enhanced by the originality and initiative shown in his approach, was ably backed up by the maturity of discussion at the viva, which his examiners described as thoroughly enjoyable. Some of his experiments were even described as ‘elegant’ in an article written about his recent publication.
My PhD research was focused on mechanisms that regulate nuclear organisation during mitosis.
The membranous nuclear envelope is no longer seen as just a barrier between the cytoplasm and nucleoplasm, but also as a main organiser of chromatin within the nucleus. Chromatin tethered to the nuclear envelope often represents repressed, inactive chromatin. Furthermore, bulk release of chromatin from the nuclear envelope occurs at the beginning of mitosis. This feature is conserved throughout the domains of life, irrespective of whether an organism performs a completely “open” mitosis like humans, where the nuclear envelope is completely broken down, a “closed” mitosis like budding yeast, where it stays completely intact or a “semi-open” mitosis, like the fission yeast Schizosaccharomyces japonicus, the subject of my studies. This release is likely important for the proper segregation of chromosomes. If and how there is an active mechanism that can dynamically regulate chromatin contacts with the nuclear envelope during interphase and how this relates to bulk chromatin release during mitosis was unknown.
In my PhD I studied an inner nuclear membrane complex, Lem2-Nur1, that tethers chromatin to the nuclear envelope during interphase. I also studied a membrane remodelling complex, ESCRT-III/Vps4. I was investigating the latter for a role in “sealing” the membrane of the nuclear envelope during mitotic exit, which is important for the establishment nucleocytoplasmic compartmentalisation. I had been seeing strange phenotypes in yeast mutants of ESCRT-III/Vps4 proteins, where Lem2-Nur1 started to cluster on the nuclear envelope. After more experiments where I acutely inactivated ESCRT-III/Vps4 and by analysis of chromatin-binding to Lem2-Nur1, we realised that the same proteins, ESCRT-III/Vps4, that regulate post-mitotic nuclear envelope sealing, also dynamically regulate the tethering of chromatin to Lem2-Nur1 and therefore to the nuclear envelope. This also had downstream effects on mitosis, preventing the bulk release of chromosomes from the nuclear envelope. These cells are very sick, and our hypothesis is that they now have problems with segregating their chromosomes.
This is interesting, as it provides a novel mechanism that can regulate chromatin-nuclear envelope contacts and also shows how proteins in the nuclear envelope can perform different functions throughout the cell-cycle.
Since completing my PhD I have joined the lab of Adele Marston at the University of Edinburgh. Here, I am studying the adaptations to the chromosome segregation machinery that allow the specific segregation of paternal and maternal chromosomes during meiosis in frog and human oocytes.
I am very honoured to have been selected for this year’s Tadion Rideal prize. I would like to especially thank my supervisor Snezhka Oliferenko and our collaborators Simon Sprenger and David Teis. I would also like to thank members of my thesis committee Frank Uhlmann, Jeremy Carlton, Dylan Owen and Baljinder Mankoo.
About the award
The Tadion Rideal prize is awarded annually to a PhD student who has carried out outstanding doctoral research in the area of molecular science. The £1,000 award was created in 1983 by Dr J Tadion to commemorate his association with the late Sir Eric Rideal FRS of King’s.