I first met David exactly 44 years ago this month, at the 1980 EMBO Drosophila Workshop in Crete. This was a meeting reserved for principal investigators to which I had somehow gained admission, despite still being a mere PhD student. As I entered the reception on the first evening, I was feeling extremely nervous and intimidated by all the senior scientists gathered around chatting in groups and was desperately looking around the room for someone who might speak to me. And then I came across David, who, with his characteristic smile, engaged me in conversation about my research interests. He immediately put me at my ease and gave me the confidence to make the most of the meeting, something I will never forget.

Eighteen months later I saw an advertisement for a research fellowship in David’s lab and did not hesitate to apply. David invited me for interview at the ICRF labs in Mill Hill, an experience that for me was both exhilarating and life-changing. We talked all day about how fruit fly embryos develop and his plans to understand the function of the “hairy” gene that he had just succeeded in cloning – one of the first of the so-called segmentation genes to be isolated molecularly. The combination of David’s razor-sharp mind and child-like enthusiasm was irresistible and I did not think twice about accepting when he offered me the post. So began three of the most exciting years of my scientific career. David’s thirst for knowledge was infectious and I could not wait to get into the lab each day to see what new phenomena we would uncover.

The joy of making new discoveries – be they inside or outside the lab – is something David never lost. Indeed, only a few weeks ago when I last visited David and Ros, his wife, in their flat in London, he excitedly told me that he had discovered a new entrance to the Barbican Arts Centre! When he explained that this was located half-way down the ramp to the underground car park, I must admit that I did wonder if his illness (glioblastoma) might be playing tricks with his memory. But I happily agreed to go for a walk with him so that he could show me – and sure enough, as we descended the ramp into the carpark, there was the door that led us straight into the entrance foyer of the centre!

David’s satisfaction at having found the best route into the Barbican from his flat was palpable, a reflection of his constant quest to find the best way of doing everything. This trait was worth its weight in gold to those who worked in his lab – he consumed the scientific literature obsessively and could always tell you the latest and best ways of doing things, often prefaced by “what you should have done”! It was David who introduced me to SP6 polymerase, which revolutionized the synthesis of probes for in situ hybridization. The fact that this superseded the single stranded DNA probes, the synthesis of which David himself had perfected with his post doc, Julian Burke, was of no concern to him – he thrived on technological progress.

Outside the lab, David could always tell you the best places to ski, the best restaurants to eat at, the best wines to drink – the list was endless, informed by his voracious appetite for reading “Which”! There was only one occasion when he got things badly wrong: I had wanted to buy a HiFi so naturally sought his advice. He told me which turntable, amplifier and speakers to buy and which audio store to buy them from, in West Hampstead as it happened, which I duly visited one Saturday afternoon. The next Monday David asked excitedly if I had got everything – “yes” I replied “and I bought a CD player too!” David’s expression immediately changed and he shook his head: “no, no” he exclaimed, “CDs will be obsolete in a couple of years when Sony launch DAT (Digital Audio Tape)” That was in 1984!

Not only was David always happy to give advice, he was also incredibly generous with his time. I recall him staying late one evening to show me how to do colony lifts of a phage library that he had helped me construct in an effort to clone the trithorax gene, something he encouraged me to do in my “spare” time. We did this in his cramped and cluttered lab-cum-office whilst listening to the Archers on the radio! Many years later, after I had moved away from the DBU in Oxford – where we had been colleagues for nearly 10 years – and established what was to become an MRC Centre in Sheffield, I asked David if he would serve on its Scientific Advisory Board. He agreed without hesitation; and most recently it was David to whom I turned when I needed an external assessor on an appointments panel for the Living Systems Institute in Exeter, a role he fulfilled with his customary thoroughness, insight and good humor.

David began his scientific career sequencing a tRNA – he has left us enriched by the qualities denoted by the much shorter sequence of a well-known restriction site, CCGG: Caring, Compassionate, Generous, Genius.

Thank you for everything David – I will miss you.

Philip Ingham FRS

Raymond Schinazi and Family Chair of Life Sciences

University of Bath

I have written many letters on behalf of numerous students to support their applications for various prizes, jobs, and positions, including several previous Beddington Medal applications. However, writing a letter supporting Delan Alasaadi for this award comes with great ease, as Delan has been an excellent Ph.D. student.

Delan developed great curiosity; he continuously engaged with his colleagues in discussions during our lab meetings and beyond. With unique ambition, he sought novel ideas to test in his project. With impeccable determination, breaking the physical barrier, he established collaborations and sought expertise across Europe and other continents, learning the most challenging techniques and valuable lessons.

Delan’s PhD thesis was about the role that tissue mechanics could play in neural crest induction. This was a risky project because of the lack of tools to measure and modify mechanics in vivo. Delan spent the first part of his Ph.D. designing biophysical tools to investigate the feasibility of the question at hand, showing great creativity in his experimental approaches. Embryonic induction is the process by which a group of cells sends signals to adjacent tissues, changing their differentiation fate. An important aspect of embryonic induction, which has been poorly studied, is how the receiving tissue regulates the response to the inductive signals—a process known as ‘competence.’ Additionally, while the molecules involved in embryonic induction have been identified, the role of mechanical cues in this process has remained largely unexplored. Delan found that during early development, the hydrostatic pressure of the blastocoel cavity increases. This increase is sensed by the ectoderm cells above the cavity, modulating Yap activity, which in turn regulates the response to Wnt signaling—a key player during neural crest induction. Thus, Delan found, for the first time, the mechanism that could explain the loss of neural crest competence during development: the increased hydrostatic pressure leads to the retention of Yap/b-catenin in the cytoplasm, impairing neural crest induction even in the presence of the inducer Wnt (loss of competence). Delan showed that this mechanism is conserved in embryos of different species (e.g., amphibians, mice, humans). This work has been recently accepted in Nature Cell Biology (2024), with Delan as the sole first author.

There are two important aspects of how Delan approaches research that make him a deserving winner of the Beddington Medal:

Fearless and ambitious: There was not a single technique or experiment that Delan did not learn if he considered it necessary to address his PhD project. Consequently, he set up in my lab many techniques that we did not have, such as micropipette aspiration, microcomputed tomography, Micro-pressure probe (servo-null) to measure hydrostatic pressure, and in vivo biophysical tools among others.

 Commitment: Not only did he work countless hours and overcome the limitations of developing his PhD during the COVID-19 pandemic, but he also showed a commitment to his work and experiments that is difficult to find. Just one example: he wanted to measure the hydrostatic pressure inside the embryo, but there are only a few labs worldwide that have the equipment and expertise to do it. He found a lab in the Netherlands that could teach him the technique, but we failed to get a source of Xenopus embryos from the Netherlands; instead, we got embryos from Belgium. So, every day, Delan had to travel to Belgium in the morning, get recently fertilized embryos that he kept in a low-temperature incubator on the train, and rush back to the lab in the Netherlands to conduct the experiments. He succeeded!

In addition to his main Ph.D. work accepted in Nature Cell Biology, he is the co-first author of another paper published in Developmental Biology about neural crest migration and the first author in a two-author review to be published in the journal Cellular and Molecular Life Sciences titled “Mechanically guided cell fate determination in early development,” written entirely by Delan.

In conclusion, Delan has been the only and mighty driving force behind his PhD work, identifying for the first time that mechanics (hydrostatic pressure) controls embryonic competence. His findings resolve a 100-year-old question: how embryonic competence is regulated, and which implications in stem cell research and cell therapy approaches? He is a motivated and dedicated young researcher, and all his efforts deserve to be recognized with an award such as the Beddington Medal. Therefore, I support this application in the strongest way possible.

• Roberto Mayor

Published work:

It is with great pleasure that we nominate Professor Petra Hajkova for the Cheryll Tickle Medal. Petra has become such an established member of the field that it will surprise many to learn that she started her lab just 14 years ago. In this short time she has risen through the ranks at the MRC London Institute of Medical Sciences (LMS) from junior group leader (2009) to Epigenetic Section Chair (2018) and on to the Interim Director (2021-2022). All the while she has continued to make the major scientific contributions that have been her hallmark since the start of her research career.

Petra’s interest in DNA methylation started while she was an undergraduate, studying the expression of integrated viral sequences. In her PhD, Petra developed bisulphite sequencing methods and applied them to study epigenetic reprogramming in primordial germ cells (PGCs), in a now classic paper, with >1300 citations (Hajkova et al., 2002, Mech Dev). This longstanding interest in, and fundamental understanding of, DNA methylation underpins her rigorous approach to investigating epigenetic reprogramming and DNA demethylation in PGCs and the zygote; in a field in which many ideas have come and gone. Her postdoctoral studies with Azim Surani further characterised changes in chromatin accompanying DNA demethylation in PGCs (Hajkova et al., 2008, Nature). In a landmark paper Petra and Azim connected DNA demethylation in PGCs to the base excision repair pathway (Hajkova et al., 2010, Science). Petra’s subsequent work has shown that, in contrast to the prevailing dogma, Tet-mediated hydroxylation is not required for DNA demethylation, either in the zygote (Amouroux et al., 2016, Nature Cell Biology) or in PGCs (Hill et al., 2018, Nature). Rather Tet proteins protect against de novo demethylation following reprogramming. Further mechanistic work in the zygote showed that continuous histone replacement is required for transcriptional regulation and epigenetic programming (Nashun et al., 2015, Mol Cell).

How the epigenome is regulated in different pluripotent states – both in vivo and in vitro – has been an ongoing interest. Petra was the first to show that mouse embryonic stem cells (ESCs) grown in 2i media exhibit global DNA hypomethylation (Leitch et al., 2013, NSMB). This study also demonstrated that mouse embryonic germ (EG) cells are transcriptionally indistinguishable from ESCs, arguing against an epigenetic or transcriptional memory of their distinct origins. More recently, with Anja Groth, Petra has developed isolation of DNA by 5-ethynyl-deoxyuridine labelling for mass spectrometry (iDEMS) (Stewart-Morgan et al., 2023, Nature Cell Biology). A versatile technique with many applications, this provided new insights into the restoration kinetics of DNA methylation in ES cells, revealing that maintenance methylation fails to keep up with cell division in mouse ES cells.

Petra has also influenced how we view the biological function of epigenetic reprogramming. Her work suggests that this process is required to enable PGCs to transition to gonocytes and prepare cells to initiate meiosis, rather than simply achieving imprint erasure (Hill et al., 2018, Nature). A more recent study revealed sex-specific epigenetic regulation and the necessity for dynamic alterations in repressive chromatin in PGCs (Huang et al., 2021, Nature). Conceptually this distinguishes epigenetic regulation in the germline, a lineage characterised by developmental reprogramming from that in soma which undergoes progressive differentiation. Overall, Petra has made key contributions to our understanding of epigenetic regulation during germline and pre-implantation development. Petra is also highly collaborative, as evidenced by an array of insightful publications across diverse fields, including myeloid cancer, microglial biology, alternative TSS usage, sperm biology and nematode evolution.

Beyond research, Petra is an excellent colleague and leader, as evidenced by her prize for mentoring and the plaudits she received as leader of the LMS Epigenetics section, which scored highly at quinquennial review. During turbulent times, she stepped up to be interim director at the LMS, where she championed the cause that fundamental research should remain central to the new strategy envisioned for the LMS. Petra’s other prizes and achievements are detailed in her CV, and we would strongly advocate that the Cheryll Tickle Medal is added to these.

• • Harry Leitch
  • Ian Chambers