Professor William Holt
SYNOPSIS OF CAREER / RESEARCH INTERESTS
I am currently a Visiting Professor at the University of Sheffield and an Honorary Research Associate of the Smithsonian Institution in Washington, DC. After obtaining my first degree in 1974 by passing the Institute of Biology membership exams, I obtained a PhD in 1979 through the Royal Veterinary College (London). I spent most of my professional life at the Zoological Society of London, where, after retiring in 2011, I became an Honorary Research Associate. In 2012 I was awarded the Setchell medal by the British Andrology Society and in January 2018 the SRF awarded me their Marshall medal.
In my research I have tried to combine studies of basic reproductive biology in various species, including many wild species, with some practical developments of reproductive technologies and their applications to wildlife conservation. Research in semen cryopreservation and semen assessment in both wild and agricultural species led me into many international collaborations; notably with Steve Johnston at the University of Queensland (Australia), where we attempted to solve the intractable problem of freezing wallaby, kangaroo and koala sperm. More recently I have collaborated with Fran Otero-Ferrer and Marisol Izquierdo at the University of Las Palmas, Gran Canaria, studying how the quality of paternal diet affects placental function and offspring survival in seahorses. (Seahorses are very unusual because the males not only produce sperm; they become pregnant as well!).
The seahorse work is an offshoot of research into the ways in which the peri-conception diet in mammals (both male and female) affects offspring development and their future wellbeing. This is an interest that developed through working with Professor Alireza Fazeli (formerly at the Zoological Society of London and now at the University of Sheffield). We realised, about 15 years ago, that sperm transport in mammals stimulates both de novo gene transcription and protein synthesis in the uterus and oviducts, thus indicating that spermatozoa are involved in establishing the appropriate milieu for future embryo development.
Since retiring in 2011, and without having to contend with the burden of administration, I have co-authored more than 40 scientific papers and have also planned and co-edited three books.
During my PhD project I had the opportunity to work with Professor Jack Lucy, then at The Royal Free Hospital Medical School, London. Professor Lucy was an expert on membrane function, including membrane fusion mechanisms. Working in his lab we were able to show that mature ram sperm, i.e. those that had passed through the epididymis, could be induced to fuse with chicken red blood cell membranes. Interestingly, the fusion process thus induced looked ultrastructurally very similar to the membrane fusion that occurs between the sperm and egg plasma membrane. It was also interesting that the immature sperm, i.e. those collected from more proximal regions of the epididymis, could not fuse with red blood cells when tested under the same conditions. The fused spermatozoa did not show any nuclear decondensation.
As part of my research was focused on finding ways to assess sperm quality, especially after cryopreservation, I was keen to find ways to measure sperm motility more objectively that the usual subjective approach that was common up until the 1980s – 1990s. After some false starts I was introduced to Professor Geoff Hobson (University of Sheffield) who had at the time (late 1980s) developed a computerized technique for tracking individual cars as they moved along roads and around roundabouts. When I provided Geoff with some videos of motile sperm, we were impressed to see that his system could track the sperm very successfully and in real-time. This observation led to some novel developments in sperm motility assessment and the commercial development of a sperm tracker, which has been used in many labs around the world.
In the late 1990s I collaborated with Professor Alireza Fazeli (now at the University of Sheffield),when we received a grant to study the interactions between oviductal cells and spermatozoa. One crucial experiment led to a really important finding: namely that after insemination, the mouse female reproductive tract modifies its gene expression profile and upregulates a new set of genes. This work was subsequently extended to the pig reproductive tract and we were able to show that the same effects occurred. These developments came at a time when microarray technologies were being developed for gene expression profiling.
I have also been privileged to undertake research in a number of wild species, where reproductive systems are not always what you might expect. Over the past 15 -20 years I have had the opportunity to investigate reproductive mechanisms in seahorses, the species where it is the males who become pregnant. This has involved valuable collaborations with a number of excellent and highly skilled researchers, from whom I have learnt a great deal.
VALUE OF SRF MEMBERSHIP
I gave my first ever research talk in 1976 to the SRF (back then it was still the SSF), and then continued to submit my abstracts to the SSF meetings for either poster or spoken presentations. These experiences resulted in much valuable feedback and, importantly, I began to know other scientists in mine and allied fields. Many of these contacts made through the SRF became firm friends, and as a result produced many benefits such as collaborations, shared grant and publishing opportunities, and also shared reciprocal opportunities for students to be hosted in the UK and abroad.