Proteomics: An Expensive Science

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By Shawn Lawrence

Proteomics is the study of the structure and function of protein, just as every living thing has a complete set of DNA known as its genome, people all carry a full complement of proteins known as the proteome. In Canada, the benefits from proteomic research have been felt in such areas as healthcare, agriculture, forestry and the environment. The understanding gained from it has lead to new insights into how different diseases might be prevented, diagnosed and treated.

From the time the first yeast proteome interaction map was published in 2003, Canada’s interest in, access to, and familiarity with proteomics technology had expanded markedly. Today, experts in this field can be found at universities and research institutes across the country and every single major university has an institute that either has a hand in proteomics as a core service or as a research activity.

In general, the basic concept of proteomics has become more mainstream, but unlike other ‘omics’, there isn’t a strong association in place or any real central unifying voice representing it in Canada. Canada Research Chair in Proteomics and Systems Biology Dr. Daniel Figeys, whose research involves mapping protein interaction related primarily to human disease as well as building technology related to proteomics has often wondered why that is.

“In Europe and in the United States there are organizations connected to HUPO (Human Proteome Organization, an international scientific organization representing and promoting proteomics through international cooperation and collaborations). Yet in Canada we are active in HUPO but we do not have such an affiliation like these other countries have,” he said.

Dr. Figeys believes that part of the reason for the lack of such an affiliation is that up until now, proteomics was never really on the centre stage of Canada life science research. As such, money for innovation and developing new proteomics technology in Canada has always been limited in comparison to the other ‘omics’, despite the fact that awareness of its potential continues to grow within the Canadian scientific community.

According to Ontario Research Chair in Biomarkers program in Proteomics and Bioinformatics Associate Professor Andrew Emili, the major reason for this is that the Canadian proteomics community is still too diverse, with generally less of a shared, cohesive vision (biological or clinical) compared to other ‘omics’.

Up until 2006, the Protein Engineering Network of Centres of Excellence (PENCE), which in 2001 shifted its focus to proteomics, was a major contributor to proteomics projects. It did much for the proteomics community in Canada, hosting an annual Canadian conference on proteomics in an effort to connect and service the broader Canadian proteomics research community. It also provided a public database of researchers, companies and centres involved in proteomics. But with its closing in 2006, there was no organization to step in and fill that void.

“We do have the Canadian Proteomics Initiative (CPI), a group that operates as an advocate or forum for the Canadian proteomics community, facilitating knowledge dissemination, networking, awareness and potential funding, but it hasn’t achieved the influence or impact of genomics or disease groups in either respect,” Emili said.

Dr. David Wishart, a professor at the Departments of Computing Science and Biological Sciences at University of Alberta and one of the founders of the Canadian Proteomics Initiative agrees with both researchers that fragmentation is a key challenge for proteomics research in Canada adding as well it’s not as unified as it used to be in Canada.

“You used to be able fit all the proteomics projects into one place because they were all affiliated with one network, but now it’s pretty much scattered in the sense that they aren’t connected, they’re all working on their own accord, and this adds to the challenge,” Wishart said.

Wishart argues that a more connected Canadian proteomics community would benefit proteomics researchers in coping with some of the challenges they are faced with, the biggest of which is funding. His hope is that with CPI that eventually a plan will be realized to set in motion the development of just such a body.

“CPI serves a purpose in that it is networking people together obviously, but it’s not paying for the operation of equipment, student salaries, staff salaries and things like that. An organization is needed for that,” he said.

As it stands now, Genome Canada and the Canadian Foundation for Innovation (CFI) are the primary funding and information resources for proteomics in Canada, with Genome Canada giving grants for the operating of projects and CFI doing the same for the purchase of proteomic equipment. Researchers also have access to varying levels of support depending on which province they are in from other organizations and initiatives but not at the same levels as they get from Genome Canada and CFI. In general, most of the projects funded by Genome Canada (operating) and the Canadian Foundation for Innovation (equipment), have done well over the past decade.

Dr. Figeys believes that both CFI and Genome Canada are doing their part to help proteomic infrastructure grow in Canada especially in universities and research centres stating that because of these investments, many universities and institutions have been able to put in place the many expensive pieces of equipment they need to do proteomics. But the problem, he adds, lies in the fact that these projects are non-renewable and thus when they come to an end of a project the equipment provided is in many instances no longer put to use. The failure to keep these projects going also translates into a critical loss of momentum.

Emili goes further on this assumption, stating that even after building up powerful technology platforms, there is no mechanism to sustain ongoing activity.

“It’s not because of lack of will on Genome Canada’s part either, but rather the way it (Genome Canada itself) gets it’s funding and in turn how it is passed onto the researchers,” said Emili.

Another one of the challenges proteomics researchers in Canada face is that proteomics is a very equipment dependent form of research. According to Figeys, before researchers at university and institutes working outside of core proteomics facilities or labs can even apply to CFI for money for equipment, they have to go through an internal political process first within their own university or institution and be selected. That can be a difficult process in itself when they are competing against other ‘omics’ based sciences, and universities tend to frown upon the expensive nature of proteomics.

“Generally proteomics is incredibly expensive so it can only be done when there’s backing or a belief that the project is an important priority,” he said.

This is another reason an organization devoted solely to proteomics is needed in Canada states Wishart, because it’s difficult to get money by conventional granting mechanisms; “The funds from conventional grants are just not sufficient to do a solid extensive proteomics analysis.”

Evolving proteomics core facilities at universities and institutes is one way proteomics researchers are coping with this obstacle, because these core facilities allow them to still obtain and maintain equipment, which in exchange they use to provide service work to academic, industrial and governmental research groups. This allows them in the end to justify the high equipment cost to the deans and the chairs at their universities and institutes, and it keeps the equipment out of mothballs.

“It’s a good way of doing things, though I don’t think there are any core proteomics facilities in Canada that actually make money, so it is not a final solution” said Wishart.

Additionally, the trend has seen a movement on behalf of CFI towards giving grants to more project and program based research rather than core labs. This has put pressure on some of the proteomics core labs because their only source of renewal is CFI. These centres thus are stuck with older less advanced equipment further hindering their ability to keep up.

“On the one hand, the breadth and depth of proteomics infrastructure and expertise has grown significantly in the past few years. On the other, it remains highly capital intensive and yet no funding process has been implemented to ensure that the existing technology base remains cutting edge and that successful projects remain at the forefront of a fast-moving field,” said Emili.

In terms of support coming from the actual biotech industry, a lot of pharmaceutical companies have stopped their proteomics programs over the past few years because it wasn’t giving them drug leads or drug hits at the rate they felt was affordable or worthwhile. Similarly, when these companies initially established their programs, the technology wasn’t as mature or robust as people had made it out to be so it was over sold and people were soured on the idea and disappointed. So now, if the Genome Canada or CFI funding were to ever disappear, it would be a pretty serious blow to activities and research in proteomics.

Still the number of programs that have components in proteomics or at least in protein research are holding and other branches of science are now reaching in to take their cut of the proteomics pie. The Agricultural Bioproducts Innovation Program (ABIP) is one such program indicative of this trend. The $145 million, multi-year program seeks to mobilize Canada to build greater research capacity in agricultural bioproducts and bioprocesses and represents an important new injection of money into proteomic research in Canada.

As for Genome Canada, it is planning on going ahead with its request for about $120,000,000 to Industry Canada for its budget and if it is supported then that too could lead to a number of new projects with many of them having proteomics as part of their work. There is also a CFI initiative that is being offered this year with many letters of intent that are going forward that could represent more opportunities for renewal and moving proteomics ahead. All of this will again depend upon what different universities put in as their priorities, so if proteomics falls of the priority list then it won’t lead to any CFI requests.

And of course the Canadian Proteomics Initiative still has the potential to further develop its relationship with HUPO. Wishart indicates that is the plan, stating that the hopes are to expand the Canadian Proteomics Initiative into the Canadian Proteomics Organization and affiliating it with HUPO. For the time being though, Canadian proteomics researchers will have to make do with the system that they have.

Figeys believes that shouldn’t be a problem pointing to Canadian researcher’s track record in the past in adapting to challenging situations.

“The whole reason mass spectrometers are around today is because people in universities would get grants that were so small they couldn’t afford to buy them, we had to build our own. We’ve always managed to do tremendous work with limited resources.”