On the Chase for Elusive Genetic Markers


The research field Eva Barroso chose for her Ph.D. is so new that even she had never heard of it before seeing the job posting on the Internet. "I was interested in human genetics, but not especially in this field," she says. What the Ph.D. project was proposing was the opportunity to try and track down genetic markers in order to predict an individual's susceptibility to diseases that involve more than one gene.

While this type of research was common for single-gene conditions, it was breaking ground for complex diseases. Barroso was too hooked on the novelty of the idea to let it go. Now a year and a half into her research project, Barroso thinks her career choice was "risky, because it is an unexplored field and you can find [either] a lot of things or nothing." But she doesn't regret her decision one bit. "I decided to do it anyway because it seemed interesting to me."

Getting on the research track

Barroso did the first two years of her undergraduate degree in Tenerife, the largest of Spain's Canary Islands before deciding to leave. "I wanted to know more places, more people, [so] I moved to Madrid," she says. She enrolled at the Universidad Complutense de Madrid and completed her degree 3 years later in 2001. "I didn't have anything in my mind at all about what I wanted to do" for a job, she says, so she decided to spend another two years at the Universidad Autonoma de Madrid on a specialisation degree in biochemistry.

After graduation, she went back to Tenerife to be closer to her family and started looking into both jobs and Ph.D. scholarships. "I [first] spent 4-5 months in a lab in a hospital," working as a technician and studying genetic polymorphisms in kidney patients. "The final goal was to do a Ph.D. in this lab, but it wasn't clear in which field--human genetics, physiology, [or] biochemistry ?" Her work experience, combined with the research project she did in the final year of her biochemistry degree, convinced her that her interest lay in applied human genetics. In the end, getting a scholarship in this lab also proved difficult, so Barroso gave up on the possibility of doing a Ph.D. at home. "[In Tenerife] possibilities to obtain a fellowship are very bad so I thought I could come back to Madrid and look there," she says.

Barroso saw an ad for "a scholarship with a project and a supervisor" at the National Centre for Cancer Research ( Centro Nacional de Investigaciones Oncológicas , CNIO) while searching for available Ph.D. positions on the Internet. "I was interested in this project [so] I contacted the CNIO," she says. The competition to get into the CNIO is tough so she was pleased when they accepted her. The scholarship, which covered the 4 years of her Ph.D., was obtained from the Communidad de Madrid with the help of her supervisor Javier Benitez, the Human Genetics group leader at the CNIO.

Tracking Down Elusive Markers

Some human diseases are caused by a drastic change in the information encoded by a single gene. But in other, more complex diseases a whole host of genes--and relatively minor changes within them--are at play. "The aim of this kind of project is to find small changes in several genes that could mean more susceptibility to diseases such as cancer, cardiovascular diseases, and diabetes," says Barroso. These changes, which may affect just one letter of the genetic alphabet, are referred to as single nucleotide polymorphisms, or SNPs. Isolated SNPs are often harmless, but taken together they may threaten human health.

Barroso herself is focusing on identifying SNPs that would indicate a greater risk of developing sporadic breast cancer. In contrast to the types of breast cancer that run in families and tend to be governed by single genes, sporadic cancer affects just one individual within a family and is often caused by multiple genes. Her research approach relies on samples from cancer patients and controls, the many SNPs databases now available on the Internet, and state-of-the-art DNA amplification techniques. She also carries out statistical analyses to assess potential links between SNPs and cancer predisposition.

What it takes to break in

One of the challenges of working in this field is that it relies on knowledge and skills from many different disciplines. "You need to have a good knowledge about molecular techniques, a genetic background, some about population genetics, and genetic epidemiology," says Benitez, whose wide experience in human genetics as a whole gives him a unique perspective on career development. Benitez says that scientists interested in the field need to "deepen [their knowledge] into the disease that they want to start working on from a clinical, genetics, and biological point of view." Barosso believes that a talent for innovation is essential. "In other fields of biology, [scientists] can follow normal techniques and do well in this field; we [must] develop new techniques," she says.

When science flirts with science fiction

The impact of such research could be huge. In the long term, Barroso says, "the idea is to have your DNA checked for [predisposition] to breast cancer, and every [other known disease]." Given that environmental factors often influence disease development, susceptible individuals could be in a position to reduce their risk of contracting some diseases.

Medicine wouldn't be the only field to benefit from such research. "The information inside SNPs [could] also [be used] for evolution studies," says Barroso, or "to study the migration of people around the world," given that SNPs vary between people relative to their origins. "SNPs are the markers of our history and of our future as patients," she says.

Still, Barroso thinks many more scientific advances will be needed before her research can be applied in real life. "This is science fiction," she says. "We need more information about the patients, the controls, [and] their life habits, because everything is related to what these genes can do in our body." And research on how these environmental factors relate to our genes, let alone our genomes, remains a mystery.

A risky career choice?

"When I looked for [a] thesis [project], I didn't know this type of research [existed]; nobody had told me about it," says Barroso. That it is so new gives little ground to base hypotheses upon. "You can succeed or fail," she says. Still, "it is risky not just for the present, but also for the continuation of my career." For one thing, these types of projects are more difficult to fund than traditional ones, she says. "You depend on statistics, [so] it could [well] be a susceptibility gene, but every time there [will be] a 'but'." She also thinks that, if she needed or wanted to change fields, it would be rather difficult because the techniques she uses are both very specific and expensive. "If this field fails, I would be lost, because nobody uses [such] techniques in a normal lab."

Would Barroso have chosen this field had she known these things beforehand? Absolutely. Not only does she find it fascinating, she also finds it easy to grab the interest of her family and friends when she explains what she does--a rare quality in a scientific job. Barroso also sees her field as expanding, which bodes well for her prospects. A while ago, "everybody wanted to work on AIDS, but now AIDS hasn't got the interest it [once] had," she says. In contrast, human genetics still has space to grow. Barroso would like to stay in this field, even if she knows this will probably mean expatriating herself once more. "In Spain, there are not many labs that work in this field," she says, "so for a postdoc I should go outside of Spain."

"It is particularly risky to choose this field," agrees Benitez, "because we are now in a transitory period, [going] from the study of one or two genes to the study of thousands. We do not have statistical or mathematical tools for [these] millions of data. However, we start a new period in the human genetics because we can study for the first time the complex or common diseases [which] will be the main task during the next years."

Follow Science Careers

Search Jobs

Enter keywords, locations or job types to start searching for your new science career.

Top articles in Careers