Life…science

The Life Scientist of the Year rushes out of the room to fetch a tissue. Her 10-month-old daughter has a cold, and needs to be cleaned so she will look her best for the shoot.
Her other daughter, a two-year-old, wants to do a jigsaw. She drags the box around after her mother, asking insistently for permission to open it.

The scientist returns with the tissue and efficiently wipes the nose of her younger child while explaining to the other that the jigsaw is for later. Then she sits back on the couch, breathes out and smiles with wide eyes at the photographer, asking, “Do you have kids?”

At work that day she would be helping to organise an academic conference, checking in with her team of 10 researchers, and writing up the results of a new discovery about the regulation of the immune system. On top of that she would need to organise a sitter for her infant, whose cold meant that regular day care was out of the question. Whatever else she had to contend with that day, her to-do list could well have been headed: life, and plenty of it.

Dr Carola Vinuesa from the John Curtin School of Medical Research is an immunologist, a team leader, a mother of two, a tango dancer, and a multiple award winner. It’s a full life by anyone’s reckoning.

In late 2008 she won the Science Minister’s Prize for Life Scientist of the Year. The accolade was delivered at Parliament House in Canberra during a glossy gala hosted by the Prime Minister.

“It was beautiful,” Vinuesa says. “It’s not just acknowledgement of the personal effort – but this is not insignificant, especially having a young family.

“It’s an acknowledgement for the whole team, for the efforts that the John Curtin School is putting in. It shows we can do world-class research and we can compete internationally.”

As a lead author on two major Nature papers in the last few years, Vinuesa already had an insight that her team’s research would have an impact.

The first of these articles outlined the discovery of a protein – roquin – that causes autoimmune diseases like lupus and type 1 arthritis.

The second showed how roquin interacts with a healthy immune system, and how previously disregarded genetic material called micro-RNAs are key to its function.

The research on immunity could lead to better treatments for the many millions of people worldwide suffering from autoimmune diseases. It could also have wider ramifications for immune-related research in general, potentially leading to new vaccines for diseases like HIV and malaria.

It was diseases such as these that first sparked Vinuesa’s ambition. In the early 1990s she took time out from medical studies in her native Madrid to work as a volunteer medic in India and then Ghana. There she experienced firsthand how infectious diseases operate at epidemic scales, and returned to her studies with the resolve to make a difference.

These diseases do impact mobility, and eventually mortality. They can be terribly debilitating and severely alter a person’s quality of life.

 
Yet the world of clinical care in developed Europe was a far cry from field work in the developing world. Vinuesa says she soon realised that more lives could be saved by researching diseases on a larger scale, rather than working on a patient-by-patient basis. This thinking led her to postgraduate study in immunology, and ultimately to join the lab of Professor Chris Goodnow at JCSMR in 2001 with funding from the Wellcome Trust Research Fellow program. 

 Yet the world of clinical care in developed Europe was a far cry from field work in the developing world. Vinuesa says she soon realised that more lives could be saved by researching diseases on a larger scale, rather than working on a patient-by-patient basis. This thinking led her to postgraduate study in immunology, and ultimately to join the lab of Professor Chris Goodnow at JCSMR in 2001 with funding from the Wellcome Trust Research Fellow program. Yet the world of clinical care in developed Europe was a far cry from field work in the developing world. Vinuesa says she soon realised that more lives could be saved by researching diseases on a larger scale, rather than working on a patient-by-patient basis. This thinking led her to postgraduate study in immunology, and ultimately to join the lab of Professor Chris Goodnow at JCSMR in 2001 with funding from the Wellcome Trust Research Fellow program. Vinuesa set to work to learn more about autoimmune diseases, which occur when the body’s defences against pathogens malfunction.

When it’s working normally, the immune system creates proteins called antibodies which are deployed to fight foreign bodies, such as viruses or bacteria.

But sometimes the system malfunctions and begins attacking the body’s own tissues. This is called autoimmunity, and is typified by diseases like lupus, which causes women of child-bearing age to suffer swollen lymph nodes, sore joints, rashes and kidney trouble.

After cardiovascular disease and cancer, autoimmune diseases place the highest burden on global health.

“They might not kill the same amount of people, but the impact on quality of life is significant,” Vinuesa explains. “Think of the amount of elderly people suffering from rheumatoid arthritis, for example. These diseases do impact mobility, and eventually mortality. They can be terribly debilitating and severely alter a person’s quality of life.”

In Goodnow’s lab, Vinuesa examined the genetic makeup of mice suffering from lupus. Using this as a starting point, she and her colleagues worked backwards to discover the protein that caused the disease in the first place – roquin.

“Roquin stops T-cells from displaying a stimulatory receptor, ICOS, that may cause the cells to attack normal body tissues,” Goodnow says. “Therefore this gene is critical in protecting us from autoimmunity – but it only takes the mutation of one letter in that gene to cripple its function and lead to autoimmune disease.”

The roquin discovery was announced to the world in Nature in 2005. Two years later that same journal published the team’s second finding on how roquin prevents abnormal T-cell behaviour when it is functioning normally.

“Our finding hinged on the fact that the activities of a normal roquin gene are orchestrated by parts of the genome until very recently considered to be junk DNA,” Vinuesa says.
The discovery centred on a form of RNA, or Ribo Nucleic Acid.

Most RNAs are thought of as messengers that carry information from a cell’s DNA blueprint so it can be written into proteins, the building blocks of cells and tissues.

But not all RNAs act as messengers. Some small, non-protein-coding forms of the material, called micro-RNAs, actually induce the decay of messenger RNAs.

“This decay leads to reduction of the expression of proteins such as ICOS,” says Vinuesa’s colleague Dr Di Yu, who performed most of the experiments leading to the discovery. “This is the first time that micro-RNAs have been linked to protection from autoimmune diseases.”

Once considered to be genetic junk, micro-RNAs are now thought to regulate up to 30 per cent of the genome, and have been recently shown to play an important role in the development of cancer and other diseases.

Vinuesa says the work opens up the possibility of using RNA interference, or the micro-RNAs themselves, in the treatment of autoimmune diseases. This is a line of inquiry that her team is exploring.

“We really think micro-RNAs are the fundamental regulators of autoimmunity,” she says. “There is so little known about these, that we’re only beginning to see the tip of the iceberg.

“The processes of making small RNA molecules can be very easy. It’s very cheap and extremely easy to manipulate, unlike normal drug development procedure.

“Obviously there are other risks. We know that small micro-RNAs sometimes have many targets. But there are ways of getting around this. There are small inhibitor RNAs we can make commercially that can be much more selective.”

The researcher says that eventually the line of research could lead to new treatments for autoimmune diseases, “which we won’t be doing ourselves, but we can provide information about the targets and the potential side effects and additional benefits.”

In addition to the Life Science prize, Vinuesa has also had success further afield. In 2007 she was awarded Spain’s top accolade for life science, the Biogen-Idec III prize. That same year she was awarded a Sylvia and Charles Viertel Senior Medical Research Fellowship, which is highly regarded in the field and comes with significant funding attached.

This was in addition to attracting funding from the National Health and Medical Research Council, in conjunction with the Garvan Institute, and from the US-based Juvenile Diabetes Research Fund.

But with all these rewards come the responsibilities of supervising a research team, and ensuring that there is enough funding in future to keep the team together. So what motivates Vinuesa to keep going?

“One aspect is purely selfish. I’m curious,” she says. “Every time we discover something there is a tremendous sense of achievement and satisfaction. I like the discovery process itself.

“These are very exciting times because we have unprecedented amounts of tools and possibilities for genetic analysis that weren’t available 10 years ago. Now we are running very fast.
“On the other hand, you do see that it’s something that could really change people’s lives and hopefully impact on people with these diseases. Autoimmune diseases affect one in eight Australians. I personally know a few people with lupus or diabetes or rheumatoid arthritis, so I think when you actually picture the people that could be benefited it also makes it worthwhile.
“Sometimes if you didn’t have that aspect, it’s hard to keep going with very abstract research. There were times in my career when I thought, well, am I doing anything to improve people’s lives? So I think that when you touch on something where you see its potential benefits, I think it’s much easier to be excited by the possibility.”
Breakout text:

Dr Carola Vinuesa on …

Research beyond autoimmunity

The antibodies I specialise in are the only ones that are good for generating memory. So believe it or not, all the successful vaccines today rely on the function of these long-lived antibodies. Nobody really understands what makes an antibody response to be long lived and of high affinity.

Our interests go beyond autoimmunity. If we manage to detect what makes the immune system supply the signals to produce these amazing, good quality antibodies, the work would have similarly important implications for vaccine development, for protection against infectious diseases. At the moment there are no effective vaccines for HIV and malaria, for example.

How much we know about our immune systems

We thought we knew a fair amount. But suddenly the levels of complexity are increasing. This is happening, for example, with the discovery that not all autoimmunity is regulated by gene transcription – by which genes are turned on or off – but by the way that micro-RNAs come into play to regulate the fate of gene transcripts, and therefore regulate protein expression. Probably we still know very little. There is a lot left to understand.

The value of science prizes

Every effort that makes science more popular counts. Prizes do bring science to the public. As opposed to sports or rock stars, scientists are not generally celebrated and people don’t know that it can be an exciting career. We need to make science more attractive. This might involve increasing the pay for PhD students, for example, and improving job security for researchers. Many people doing science are very bright, but it’s a hard option. There has to be more investment.