Dynamic duo in field of stem cell research

Eminent biologists talk about the highlights of their research in S'pore, and working together.

SINGAPORE - Professors Davor Solter, 72, and Barbara Knowles, 76, are well-known developmental stem cell biologists who retired recently after a five-year stint in Singapore.

The couple moved to Singapore in 2008 to set up and lead the Mammalian Development Laboratory in A*Star's (Agency for Science, Technology and Research) Institute of Medical Biology (IMB).

Prof Knowles, who got her PhD from Arizona State University in the United States, did her postdoctoral fellowship in the Department of Genetics at the University of California at Berkeley.

She is known, among other things, for her work on the role of immune response and tolerance to a particular antigen - a substance which causes an immune response by the body - in tumour formation.

Prof Solter, who earned his medical degree and PhD from the University of Zagreb in Croatia, has made significant contributions ranging from the role of cell surface molecules in regulating early development to the biology of embryonic stem cells, genomic imprinting, and cloning.

On top of research, one of the duo's most important contributions here has been training the next generation of young scientists.

Through their commitment and dedication, many early career researchers and students have benefited from their guidance and mentorship, said A*Star in a statement.

For instance, it said, two postdoctoral researchers from the Mammalian Development Laboratory - Dr Lim Chin Yan and Dr Daniel Messerschmidt - cinched competitive positions in IMB and the Institute of Molecular and Cell Biology, a key step for early career researchers towards conducting independent research.

Prof Knowles was awarded the A*Star most inspiring mentor award last year for nurturing young scientists.

Both scientists retired in June and have returned to the US.

Q: Before coming to Singapore in 2008, you had lived in different continents for 16 years. What has it been like working together?

Barbara Knowles (BK) (laughs) : Yes, this is the first time we've had a lab together in recent years. We always quarrel; scientists can never agree with one another.

Davor Solter (DS): We have different skills; I don't like to write or correct people's papers - if they already say what they need to say then that's enough. Barbara likes everything to be perfect. My style is to let people do whatever they want and learn for themselves, while Barbara advises them and tells them if she thinks their idea is a waste of time.

Yes, the two of us have disagreements but you know how people are, one will eventually give way to the other. We're not like those husband- and-wife teams who do everything together. We probably share about one-third of our publications, but we also have completely separate interests.

Q: Does this extend to your private lives?

BK: Oh yes, for instance, I like movies, Davor likes fiction. I got rid of all my old scientific papers, but Davor has his entire collection here which he shipped from the US, dating back to reprints before the photocopier was used. He is leaving this collection here in Singapore for others to use.

DS: We read different books, watch different movies. We certainly go to a lot of things together, even if one of us doesn't like it. When we go to the movies, for example, we might each watch a different one and meet for drinks later.

Q: As eminent stem cell biologists, what does your work involve and what are some of the highlights in the field to look out for?

BK: We are interested in the events that happen just after a sperm fertilises an egg to form a new life. We all know that an individual is a product of the genes he inherits but there are also processes that affect whether or not certain of these genes are expressed into adulthood.

We have been working to unravel when and how these processes occur in embryos before they implant into the uterus and we use mice as a model for human health and disease.

One of the biggest highlights of our research in Singapore for me came from studies on the embryos obtained from female mice we had been working on for several years before we came here, and just could never quite understand our experimental results. The genes in sperm and eggs are the same but certain of these genes are never expressed in sperm and others are never expressed in eggs, because they are methylated (a biochemical process).

We used embryos from females of this mutant mouse strain to identify the molecules which preserve methylation of these genes in the embryo immediately after fertilisation.

This came from a lot of difficult experimental work on single cells.

Two of our IMB (Institute of Medical Biology) postdoctoral fellows collaborated with another postdoc from our collaborator's lab in IMCB (the Institute of Molecular and Cell Biology) to solve this problem.

These results are about to be published in the highly acclaimed journal Science.

We are entering an era in science where the genome can be rather easily manipulated and stem cells are starting to be tested to replace diseased cells in whole organisms.

This is very complicated technology and the role of epigenetic changes in regenerative medicine is just starting to be explored. It is a fascinating time to be working with embryos and stem cells.

DS:  Scientists are almost succeeding in making sperm and eggs out of embryonic stem cells, the cells that can transform into any cells that the body needs. I also think that researchers will be able to create an artificial placenta. It means every person regardless of age will be able to have children.

Q: What do you think of the level of science at A*Star (the Agency for Science, Technology and Research)?

BK: It's excellent in pockets. It's been so wonderful watching the groups in this newly formed IMB doing world-class work.

DS: Singapore has the intention of becoming a scientific power, and in terms of objective parameters, it is doing really well. Unless Singapore totally stops funding science, I expect it will do very well.

Q: What about the push towards turning discoveries into money-spinners - some would say at the expense of fundamental research that is done for the sake of increasing knowledge?

BK: A*Star's vision in the beginning was broader. It would have worked but they needed to give it more time. The scholars who've been sent overseas to work in the best basic science laboratories in the world are now adjusting to the fact that there aren't so many pure research jobs for them here now.

DS: I think there was a miscalculation in the beginning and the authorities were expecting that the returns would come much faster.

And when this didn't happen they said people are just sitting on their hands, let's squeeze them a bit.

But we must look at biomedical sciences research here and how it can contribute in the right context.

It's not a matter of, say, producing a smaller, better phone. It's more like going to the moon. Cancer, for instance, is not a technological problem that can be solved by throwing money at it.

In our field you do not know where the discoveries are going to take you, but they're rarely directly translatable into something you can produce and sell tomorrow, and you can never predict which basic biological research discovery will be useful in five years, or 50 years. In any case, my guess is that the scientists will find a way to sneak in some basic research.

ailien@sph.com.sg


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