Covering the bioinformatics niche and much more

SciView Part 3: Interview With Jeremy Squire

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The SciView project continues. This time the interviewed was Dr Jeremy Squire, from the Ontario Cancer Institute, which by some freaky coincidence is where I work. The two previous interviews were with scientists, if not completely, somewhat related to bioinformatics. Not this time.

With this interview the first cycle, which I might call inaugural cycle, is complete. I would like to thank everyone for their support and if you have any comments or ideas just drop me a note. Probably in the coming months, SciView will have a home for itself and added features.

You have started your scientific career with conventional cytogenetics and doing analysis with optical microscopes. What have changed since you started, with the advances in technology. new methods,new equipments? Do you still believe that basic cytogenetics analysis is still strong?

JS: The big advance was application of CCD cameras and the computer interface to the scopes. The basic analytical platform is still 70% determined by the human brain as computers are unable to interpret the biological and technical variables of banded metaphase preparations correctly.

The other big advance was the development of FISH methods and the parallel availability of the toolbox of probes and techniques created by the human genome project. This has enhanced rather than replaced my area so that basic cytogenetics has wider applications now, than in 1973 when I first started looking at human chromosomes.

How important is bioinformatics for human genetics and oncology? With the ever increasing presence of computers in any research, how do you see the introduction of bioinformatics in your field?

JS: Bioinformatics in its various forms has played a vital role in bringing all the “omics areas” back to the bench and it is an essential ingredient in most new hypothesis driven lab projects in genetics and oncology. Like most scientists brought up on wet bench research I have a high level of skepticism of in silico projects that do not touch down to test simulations and speculations by experimental methods. This has been a weakness on some grant proposal that I have reviewed in recent years. I my field I have covered past and present issues above. In the future I see bioinformatics helping understand the 3 D structure of genomes (in cancer and normal nuclei) being essential.

Another question that is already favourite of this interview series is about computer graphic interfaces. Clearly for your type of research the graphic interface is a must have, especially in cytogenetics and microarray applications. Based on your experience would you say that the adoption of an application in your lab could be determined by the quality of its graphic interface? What do you and your group look for in a program and its graphic interface?

JS: Absolutely agree. The graphic interface has to mirror the scientific thought processes that we use when we conceptualize the data. Our experience with the Agilent array platform has been great and it has helped up move faster in integrating different genomic findings. Apart from the overall output being elegant and easy to understand it should be transparent and adaptable to our own needs. Also in more practical terms – working on Apple and PC would help a lot. Plus being able to take on your own laptop to play with whilst waiting at airports (I have done that a lot this month!)

What is your take on the main differences of oncology research between US and Canada? It seems that Canada even with a smaller number of research institutes have the lead in different fields of cancer research.

JS: In human cancer Canada has a stronger programs in signaling cancer research and cancer stem cell approaches. This relates to successes in the 1960s (stem cells) and then in the 1980s (signaling). Cancer genetics and genomics is stronger in the US, as is translational cancer research. Our funding system favours individual PI driven projects that tend to be more basic. Our genome project was poorly supported in the late 1990s. We need to have NIH SPORE grants for clinical cancer research projects as these encourage team approaches of scientists and clinicians to work together. Canada is excellent in model organism (mouse, flies, yeast) approaches to cancer research. The weakness in applied cancer research in Canada is that the bench to bedside work is used to raise money from donors but there are few Canadian success stories to talk about.

You are still in Brazil doing a sabbatical. From what you have seen of Brazilian research, how do you compare the science in a country under development, with a young science sometimes underfunded, and the science in major centres like US, Canada and Europe? What is the main advice for a young scientist who wants to come to a major centre?

JS: This is a big topic and I would prefer to talk to you about it over a beer! I think any serious Brazilian scientist has to do a postdoc in NAmerica or EU. If they love Brazil more than they love research they should develop some serious political connections with FAPESP before they leave to do their postdoc. This will help them when they come back. However it will always be frustrating to do good research in Brazil. Too many PIs here are not serious about research.

I asked this question to Joe Felsenstein and Brian Golding: How do you see the “publish or perish” in science, with the increasing number of retracted papers, fake results, rushed publications and sometimes publication of extremely similar results in different papers and journals? What are your views, especially in a very competitive field as oncology?

JS: As long as grant panels judge researchers by productivity this situation will not change. To address this area I support the idea of declaring the identity of the reviewer of your grants or your submitted paper. I think more thought would go into the review process and to the quality of submitted papers if the process was more transparent. Some journal are doing this now. In the oncology field I would like some of the journal to have part of the abstract devoted to the translational component of the study.

Do you have an advice for the young researcher in human genetics? Should s/he focus on a determined trend or be a generalist in the field?

I think this entirely depends on how the young researchers own neurons are wired. Some people function better as generalists and others need focus. There are of course intermediate versions. I would advise someone starting out to be opportunistic and to look very closely at emerging trends for the choice of a postdoc for example.

What in your opinion is your most important publication?

AS STUDENT: 1. Godbout R, Dryja TP, Squire JA, Gallie BL, and Phillips RA. Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma. Nature. 304: 451-453, 1983. AS PI: 2. Kolomietz E, Al-Maghrabi J, Brennan S, Karaskova J, Minkin S, Lipton J, and Squire JA. Primary chromosomal rearrangements of leukemia are frequently accompanied by extensive submicroscopic

deletions and may lead to altered prognosis. Blood. 97(11): 3581-3588, 2001.

I would like to thank Joe Felsenstein, Brian Golding and Jeremy Squire for taking their time to answer my questions. SciView will be back (hopefully) soon.