Bacterial proteomics attracts grant

One of the biggest ARC Linkage Project grants in the recent round has been awarded to University of Sydney microbiologist, Dr Liz Harry, to work with Australian proteomics pioneers, Proteome Systems, on bacterial proteomics.

The aim of the project, which has received $600,000 from the ARC in addition to an equivalent in-kind contribution plus additional funding from Proteome Systems is to identify cell cycle proteins in bacteria that could be used to develop novel antibiotics.

"With the increasing prevalence of antibiotic-resistant bacteria and the imminent threat of bioterrorism there is an urgent need for new targets for antibiotics. The old targets are becoming insensitive to current antibiotics and new approaches like ours are necessary to address the problem," said Harry, who uses the spore-forming Gram-positive bacterium Bacillus subtilis to study bacterial cell cycle regulation and cell division. "The reason it's good to target cell cycle regulation proteins is that many are essential and many of these proteins are likely to make important links with other essential processes in the cell, such as growth and DNA replication. Proteomics is really an excellent way of identifying targets since the actual proteins themselves are the targets, not the genes."

Harry said B. subtilis is a useful model for the study as synchronous cell division could be achieved in the first cell cycle after spore germination. It produces unique and clear-cut results that would otherwise be difficult or impossible using asynchronous cell populations. And her research using this organism has already suggested that the early stages of DNA replication are linked to the initiation of cell division.

According to Harry, the grant developed from a pilot study carried out last year by an Honours student in collaboration with Proteome Systems. This study identified, for the first time, several candidate targets. One of these proteins had long been suspected by Harry to play a role in cell cycle regulation process, confirming the utility of the proteomics approach.

"This made us all very excited that in such a short time we had meaningful results," she said.

Proteome Systems CEO Keith Williams agrees. "As with many of our proteomics discovery projects, even the initial results were very exciting, leading to a patent application" he said.

Now the project will be expanded and developed to really get down into the nitty-gritty proteomics. Part of the project will be the expansion of an existing program within Proteome Systems on membrane proteins, and low abundance proteins.Proteome Systems is already a leader in this space and the collaborators expect to produce results on a new suite of proteins not before seen.

"In the first year, what we want to do is expand the proteomics to identify as many proteins as possible that are potential drug targets using soluble fractions. We will also start to develop the techniques to look at low abundance proteins," said Harry.

"Realistically, in our second year we'll delve into other fractions - we believe some regulators will be low abundance and some will be associated with membranes and so on. Membrane protein fractions haven't been well developed for this type of bacterium but we expect the Proteome Systems' techniques to quickly produce good results"

Harry expects the project to be very collaborative, with both partners providing expertise and ideas. "We've combined my microbial expertise and their proteomics expertise."

According to Proteome Systems' Williams, the company will be able to keep the focus on developing potential drug targets. "The discipline we bring is that we're obsessed with products," he said. "We have a lot of partnerships, we're broad over the space, so we can think about how to leverage off this research into other products too."

Ultimately, the Linkage grant will allow Harry to expand into an important area of research with the support of an interested and outcome-focused partner.

"I couldn't do a project of this scope on my own. I don't have the extensive proteomic expertise required, not many people do! I also couldn't get this kind of money on an ARC Discovery project grant," she said.