In the right place, at the right time

It was the mid-1990s, a young student started his undergraduate study at the National University of Ireland Galway with a settled idea that he is going to become a biochemist after graduation. He majored in Chemistry and Mathematics in the second year. He was very down the line to receive his Honours Degree in Biochemistry and to achieve his goal.

Now we almost reached the end of 2021, but somehow still in the middle of a global pandemic. Dr. Donncha Dunican is sitting opposite me and telling me what happened later made him decide to become a molecular biologist and bioinformatician who focuses on determining the mechanisms underlying de novo and maintenance DNA methylation instead.

It was a summer internship in his third year. He was offered a scholarship to work in a microbiology lab doing recombinant DNA technology. He was intrigued by the idea that he could join together DNA molecules from two different species and manipulate gene expression. After that summer he decided to do a Ph.D. in an area that is more closely related to that specific field. But just like most of us who are starting our Ph.D., he only had a brief idea of what he wanted to do and what he didn’t. He was interested in the molecular mechanism behind cancer, however, he was not satisfied to only study the relationship between one specific gene and cancer. The Mid-90s was the era molecular biology technology took a big leap. Genetic sequencing has broken through the bottleneck and the Human Genome Project was in full swing. Scientists were equipped with much more sequencing power than ever. Donncha was at the right time to start his Ph.D. project which focused on discovering alterations in epigenetic regulators between familial and sporadic colon cancers. He was able to study multiple genes in parallel. In fact, he looked at the expression of 30,000 genes in cancer cell lines using a very early form of microarray DNA profiling technology. To this day he still remembers the big turning point in his research interest in 1998. He found an exciting paper on transposon integration screening in Saccharomyces cerevisiae to present at a journal club (Ross-Macdonald et al., 1999). The fact that you can do the screening of 10 thousand open reading frames in a matter of a few weeks ‘completely blew his mind’.

Changing his career direction into becoming a molecular biologist was most certainly a bold but tough move while his decision to dig deep into the bioinformatics world was not. He did start his research career during the time when high throughput sequencing became more accessible and there was an urgent need to understand this deluge of sequencing data. He, however, did not decide to become a bioinformatician solely for that reason. Unlike me, who chose to learn some coding after entering university just in case she ever needs it, he started coding from a very early age. The magic happened when he was about 10 years old. His father, who was a professor in Microbiology, decided to bring home a first-generation Macintosh personal computer during Christmas break so that his sons could try some coding. Donncha fell in love with coding ever since. During his time as a Ph.D. student, his supervisor reminded him of his strength in computing and he has not forgotten it ever since. He is improving his coding skills even these days. In his opinion, the real advantage of doing the bioinformatics yourself is the control of the analysis and that you will always learn something new along the way. The benefit of learning bioinformatics can also apply to people who mainly focus on wet lab work. He has also encouraged his previous students to pick up a programming language like R because it is ‘pretty intuitive’ even to non-programmers. We are lucky at the Institute of Genetics and Cancer with the support of a core bioinformatics team. But we may not find the same luxury in a different institute. Asking someone else to analyse your data could also involve a lot of communication and time, which may not be available in some circumstances.

With the interest in epigenetics developed during his Ph.D. and his computational skills, he sailed on to start his postdoc in Scotland with Prof. Richard Meehan and stayed in academia ever since. He is studying the effect of the LSH protein in mammalian systems. Depletion of the LSH gene leads to severally less methylation in the genome. The protein, however, has no domain that might be expected to deposit DNA methylation or to regulate DNA methylation in an obvious way. How does a non-canonical DNA methyltransferase control DNA transcription? This intriguing research question has led to multiple research outputs (Dunican, Pennings & Meehan, 2015; Dunican et al., 2013).

I was interested in how he maintains his work-life balance. Growing up in an academic family, and his wife also works in a science-related field, they support each other’s careers. They understand and accommodate weekend work in the lab or curriculum preparation. He did his Ph.D. in a medical school that is off-campus which was closed on Sundays and only open for 4 hours on Saturday mornings. On a normal weekday, security will still try to get everyone out of the building by 9pm. In one way it was a good thing, it forced him to carefully plan his experiments and make learn time management.

At the end of the interview, I asked Donncha if he wants to share some advice with the newcomers this year. The first piece of advice is to not panic if you think you are reaching the end of one timepoint in your Ph.D. but you do not have enough data on hand. Many people (including himself!) often learn ‘what not to do’ and all the possible mistakes in the first year of their Ph.D. – but they learn and gain more maturity in the second year. The final year is to put what they learnt into real action. “It will all come together at the end and it always does.” The second piece of advice is to not be afraid to stick up for yourself and to take ownership of your project. Never be afraid to voice for yourself because at the end of the day it is your own research project. The last advice is that to think about career options at an earlier stage because the academic pyramid is getting steeper all the time.

References:

Dunican, D.S., Cruickshanks, H.A., Suzuki, M., Semple, C.A., Davey, T., Arceci, R.J., Greally, J., Adams, I.R. & Meehan, R.R. (2013) Lsh regulates LTR retrotransposon repression independently of Dnmt3b function. Genome Biology. 14 (12), R146. doi:10.1186/gb-2013-14-12-r146.

Dunican, D.S., Pennings, S. & Meehan, R.R. (2015) Lsh Is Essential for Maintaining Global DNA Methylation Levels in Amphibia and Fish and Interacts Directly with Dnmt1. BioMed Research International. 2015, 1–12. doi:10.1155/2015/740637.

Ross-Macdonald, P., Coelho, P.S.R., Roemer, T., Agarwal, S., Kumar, A., Jansen, R., Cheung, K.-H., Sheehan, A., Symoniatis, D., Umansky, L., Heidtman, M., Nelson, F.K., Iwasaki, H., Hager, K., Gerstein, M., Miller, P., Roeder, G.S. & Snyder, M. (1999) Large-scale analysis of the yeast genome by transposon tagging and gene disruption. Nature. 402 (6760), 413–418. doi:10.1038/46558.