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Mark Baker on Proteomics in Australia and How He Got Into the Field

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At A Glance

Name: Mark Baker

Position: CEO, Australian Proteome Analysis Facility, Sydney, since 2003

Professor of Proteomics, Macquarie University, Sydney, since 2003

Background: Director of Biomarker Discovery, LumiCyte, 2001-2003

Foundation Director, Gynaecological Cancer Research Center, Melbourne, 1998-2001

Associate Professor, University of Melbourne, 1998-2001

Associate Professor, University of Wollongong, Australia, 1992-1998

Research Fellow, Australian National University, 1988-1992

Postdoc, Monash University, Australia, 1985-1988

PhD, Macquarie University, 1985 (worked with Janusz Gebicki on protein oxidation mechanisms)

BS in Biochemistry, Macquarie University, 1981

 

How did you get involved with proteomics?

I followed proteomics from its very birth; I was a PhD student at the time Keith Williams was recruited to Macquarie University. My introduction to proteomics was when Keith first floated the idea almost exactly ten years ago. That concept was raised when Denis Hochstrasser and Ian Humphery-Smith and Keith Williams and their teams collectively, in Sydney, started talking about high-throughput 2D gels and [protein] identification using mass spec and combining that under the auspices of the name “proteomics.”

What I was working on at the time was the oxidation of proteins, working with a radiation chemist called Jan Gebicki. He is still a professor in the same department that Keith Williams was in, biological sciences. Jan had been working on lipid and protein oxidation for many years. I was very interested in looking at the oxidation of proteins in vivo. I would take the proteins out of various tissues and try and map what proteins were oxidized. I’ve pursued that type of work ever since. I have been looking at the role of proteins and protein oxidation and the function of proteins when they change their shape or change their posttranslational modifications.

After [finishing my PhD], I spent a four-year postdoc working in connective tissue research. After that, I went to the John Curtin School [of Medical Research at the Australian National University], where I worked in a cancer and inflammation group. Then, I took an aca demic appointment, teaching molecular cell biology at the University of Wollongong, and started raising a family. I was a very keen surfer, so I wanted to move to a place [near] the beaches. I accepted a tenured university position there. But one thing that was always in the back of my mind was the need to develop an institute that was using protein discovery or proteomic technologies to try and work on early detection and the key proteins that were involved in malignancy.

About six years ago, I moved to Melbourne and set up a new women’s cancer center at the Royal Women’s Hospital at the University of Melbourne. We applied only proteomic technologies to the discovery of the key molecules involved in malignancy, ovarian cancer in particular, trying to identify early markers of ovarian cancer. We used primarily 2D gel-based approaches then.

I got an interest in SELDI technology while I was setting up that facility and then moved to LumiCyte [in Fremont, Calif.] to work with Bill Hutchins, the inventor of SELDI. That was one of the highlights of my career. I had such a fantastic time because Bill Hutchins had hand-picked 50 of the brightest scientists from around the world in all sorts of disciplines—computer science, algorithm development, chip manufacturing, chemistry, clinical trials. I worked there for two years. Then I was offered a position to come back home as the CEO of APAF.

What have you done so far as CEO of APAF?

We restructured the way in which we managed APAF, [involving] a significant change in the laboratory organization. We also went to the university and asked if they would build a new biomarker discovery laboratory, which they agreed to do. In fact, as we speak, they have knocked down a major part of the old labs where proteomics were first formed and are creating a brand-new AU$1.3 million biomarker discovery laboratory [to be opened in late September.] APAF of course has brand-new laboratories that were opened a few years ago, but this is the extension of the original lab.

APAF is not just at Macquarie University. It actually has four nodes. While APAF I, which was the original version of APAF, was just at Macquarie, the new limited company is in four sites: It’s at Macquarie University, Sydney University, the University of New South Wales, and a company in Adelaide that we work with, TGR BioSciences.

What technologies is APAF working on?

We are very actively developing technology on three fronts at present. The first is the removal of high-abundance proteins. We have been given a major grant for looking at technologies that can remove abundant proteins. We are using chicken antibodies to do that — we have teamed up with Australia’s largest egg producer, Pace Farm. They make some very interesting value-added egg products in Australia, [for example for a cake] called Pavlova that’s made out of egg whites. It was named after Anna Pavlova, the ballerina, when she visited us here. Equally, we decided that fractionation, subcellular fractionation for example, is another critical aspect and [we have] been pushing that work very deeply with Bio-Rad. [Finally], APAF has invested hea vily with LumiCyte and with Applied Biosystems to try and find ways in which we can increase the sensitivity of the higher-throughput mass spectrometers, in particular MALDI TOF/TOF instruments like the ABI 4700.

Are you also conducting research?

Well, the best way to show a product works is to put good research behind it, isn’t it? We have already had a very strong bacterial pathogenesis program going, and that has continued and grown.

There are two other [projects] at the APAF headquarters node. One is cancer. I brought that program in myself. My interest has been for many years to identify those proteins that are the linchpin proteins in driving cells from benign cancer into malignant cancer. Benign tumors don’t kill you of course. The switch to malig nancy is what kills you, the ability of tumors to spread to organs that compromise you quite easily. So if we can find the proteins and protein fragments and potential biomarkers that distinguish between benign and malignant disease, these are the molecules that differentiate what’s important clinically. We are focused on ovarian, breast, prostate, and colon at this stage.

The third area we are working on, which is very important to Australia, but probably not so much to the rest of the world, is identifying what are the key protein traits of productive crops in Australia, and in particular wheat. We have been determining how [certain] proteins are responsible for certain qualities in wheat, for example how a good quality bread is made. We are trying to map the proteins that correlate with those quality traits.

How is APAF funded?

We have two years’ funding remaining in our second round of grants. We are funded by the government, but we have to bring in funds that match those government funds dollar for dollar. The grant was AU$16.25 million over a 5-year period, and we were expected to bring in AU$16.25 million to match that. And for the first time, APAF has managed to exceed the expectations of what income it would bring in, [through] fee-for-service work, contract work, collaborative R&D schemes. These funds are added to the first round of funding that APAF got, which Keith Williams secured, AU$6.25 million. State governments have put in small amounts as well. Overall, the investment that’s gone into APAF is getting close to AU$50-60 million. The profits are distributed on the basis of where the nodes generate the profits. Some of the profits from headquarters are distributed amongst the nodes, but the majority of intellectual property discovered by each of the nodes is held by the nodes.

What’s the next thing you want to tackle?

The most important thing for APAF in our upcoming year is to find a new chairman, to get a very active dynamic researcher with some industrial savvy as our new chair. If we can get someone who is as good as Geoffrey Grigg, [our current chair who has indicated he will retire when we find a suitable replacement], we are going to be in very great shape.

Where do you see APAF in five years from now?

I think it will hold intellectual property and license it to various companies and international distribution networks. I think it will be generating intellectual property in the areas of agricultural productivity, cancer, and bacterial pathogenesis. It will remain providing services to the Australian and international research communities, because that’s part of the fun of it, having people who have a certain amount of proteomic expertise but can’t quite get the solution, and they come to APAF and then they go “aha.” It’s like a revelation, all of a sudden the curtain is removed over their eyes and they realize that they can get the answer.

It’s like that thrill of discovery. That’s why I am doing what I do for a living. I got into science in the first place because my father died of a heart attack, and he left seven kids fatherless. He was 35, and I was the oldest with the family, so I wanted to get into studying how we could protect young men from dying of heart disease. And I am still motivated by that. That’s one of the great things about working at APAF. You never hear the intangibles. The people that we work with are our greatest asset. We have a fantastic spirit at APAF. It’s the best place I have every worked and it’s a pleasure to come to work and deal with those people.

 

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