When molecular biologist Agnieszka Chacinska left her native Poland in 2001 to take a postdoc, she had a dream of returning some day to set up a lab -- but she wanted to do it in conditions comparable to what scientists experience in wealthier countries. As she built a small research group in Germany a few years later, she retained her faith that eventually she would be able to return home without compromising her science.
"That was perhaps naïve, but at the end it turned true," Chacinska says. Last November, she returned to Poland to take a group-leader position at the International Institute of Molecular and Cell Biology (IIMCB) in Warsaw, utilizing returning grants from the Foundation for Polish Science (FNP) and the European Molecular Biology Organization (EMBO). It is "a very good position and in a very nice institute," and the funding is excellent, she says. She admits her situation isn't typical for Polish scientists, but she expects, or at least hopes, that with ongoing reforms in the country, her circumstances will soon become unexceptional.
Stepping into a hot field
Chacinska earned a 5-year first degree in biology from the University of Warsaw then followed it up with a master's degree in molecular biology. She did her master's degree research project at the Institute of Biochemistry and Biophysics (IBB), also in Warsaw, looking at the effect of genetic mutations on the function of an enzyme involved in the biosynthesis of heme, using Saccharomyces cerevisiae as a model organism.
The enzyme Chacinska was looking at is located within the inner membrane of mitochondria -- intracellular units best known as cells' power plants. Developing an interest in these small organelles, she went to pursue doctoral research in the laboratory of Magdalena Boguta at IBB, searching for proteins involved in the regulation of protein synthesis within mitochondria.
Elisabeth Pain also reports on the reforms of the Polish science funding system this week in Science (subscription required).
Unexpectedly, Chacinska found that a cellular chaperone called Hsp104 was able to affect the mitochondrial protein machinery. Mitochondria are made of a thousand or so proteins that are constantly being renewed. The vast majority are synthesized elsewhere in the cell then imported into the mitochondria where they are folded and assembled. Chacinska hypothesized that Hsp104 is involved in the transport of these proteins into the mitochondria. To test her hypothesis, she visited the laboratory of Gottfried Schatz at the University of Basel, Switzerland, with a short-term fellowship from the Federation of European Biochemical Societies (FEBS) and support from the host laboratory. She spent about a year there.
Her hypothesis turned out to be wrong -- but her work put her onto another interesting topic. It was the 1990s, and outbreaks of mad cow disease in cattle and Creutzfeldt-Jakob disease in humans were making headlines in newspapers worldwide. Prions -- infectious agents made up mainly of misfolded proteins -- had been implicated in the diseases. At about that time, prions were also discovered in yeast, though in yeast they were mostly innocuous. Yeast prions were subsequently shown to be controlled by Hsp104 levels, "thereby linking the phenomenon of yeast prion with mitochondrial synthesis," Chacinska says. It was a new way of thinking that she "found absolutely fascinating," she says. Chacinska eventually demonstrated, back in Warsaw, that prions were involved in Hsp104 effects on mitochondrial protein synthesis.
The Schatz lab escorted Chacinska from one of science's many moderately trafficked byways onto a scientific superhighway. She entered a hot research field in a world-class laboratory full of ambitious, driven scientists from all over the world. "I realized that ... science is really a very international thing [and] that it's also quite competitive." Her research took on a new direction and a new urgency.
Getting to know TIM, TOM, and MIA
Chacinska finished her Ph.D. in 2000 and then, fascinated with the mechanisms governing the import of precursor proteins into mitochondria, joined the lab of Nikolaus Pfanner at the Institute for Biochemistry and Molecular Biology in Freiburg, Germany. Her work there was supported by a long-term FEBS fellowship.
Precursor proteins have to cross two membranes to reach the inside of the mitochondria. Their passage is mediated by specialized membrane complexes called translocases. In the Pfanner lab, Chacinska studied the communication between translocases in the outer membrane, called TOM, and others in the inner membrane, called TIM. "As a postdoc in my lab, she discovered the first direct connection between the preprotein translocases of the mitochondrial outer and inner membranes and showed the dynamic behavior of mitochondrial membrane translocases," Pfanner writes in an e-mail to Science Careers.
Toward the end of her postdoc, Chacinska identified a protein called Mia40, whose role was to transport precursor proteins to the space lying between the outer and inner membranes of mitochondria. She was the first person to do so. What's more, a tweak Chacinska made to a standard experimental protocol allowed her lab to become the first to discover a mitochondrial protein transport mechanism based on the recognition of newly formed disulphide bonds. This discovery "was made completely accidentally," Chacinska says. "At this stage, nobody was thinking that there are really disulphide bonds in mitochondria."
Pfanning says it was clear that Chacinska's motivations and skills were just right for a successful career in science. She "was dedicated to solv[ing] challenging problems with the right combination of creative planning and consequent and critical evaluation of experiments," he writes in an e-mail. "The scientific questions and the fun in addressing them were always the first priority for her (and not the thinking about a career). That is exactly the right attitude for making a great scientific career."
In 2004, as she was finishing writing her postdoctoral papers and expecting a daughter, Pfanner offered Chacinska the opportunity to start a small group to investigate the MIA pathway in collaboration with his own lab. "We have a great system at the University of Freiburg with collaborative research centers that stimulate the early independence of young scientists ... yet at the same time provid[e] them with mentoring by senior colleagues," Pfanner says. She could have gone looking for an assistant professorship at that time, she says, "but because I was also having just at that moment a very small baby," she chose "a slightly easier way."
Chacinska returned to Pfanner's lab in mid-2005 as a junior group leader and put together an independent team comprising one technician, four undergraduate students, one Ph.D. student, and two postdocs. These years proved "very productive, and I could really start to build maturity as a scientist ... in quite a comfortable situation," she says. She did important work, Pfanner says: "Her findings" on the MIA pathway have "stimulated the studies of many other groups that now work on this machinery."
After a couple of years leading her own quasi-independent lab in Germany, Chacinska felt ready for her next step and started looking for openings back home. "Up to now ... [in Poland], not so many scientific institutions advertise" positions and recruit the best people for them, she says. But she was able to find a position at the "very modern" IIMCB. Launched in 1999 with the support of UNESCO and the Polish Academy of Sciences, IIMCB is one of few institutions in Poland with an international advisory board and an open recruitment process.
Last November, Chacinska started setting up the Laboratory of Mitochondrial Biogenesis in Warsaw with a "very generous" Welcome Grant from FNP, an EMBO Installation Grant, and a research grant from the Ministry of Science in Poland.
With the MIA pathway now well understood, Chacinska plans to move away from transport mechanisms toward studying "how important the MIA pathway is for mitochondria and for the whole cells," she says. Her group will focus on the biogenesis and homeostasis of mitochondrial proteins and add mammalian and human cell lines to current yeasts. Just 4 months in, 12 people are already working in the lab.
Chacinska now believes she can be as successful in Poland as she could have overseas. Her optimism stems partly from reforms the Polish government is introducing into the national science system. Following the direction set by institutes like hers and efforts by FNP to propagate international standards, the government is making a push for increased competitiveness. Such changes, Chacinska says, "are crucial for proper development of science and science-based technology." She hopes such reforms will create new opportunities in Poland for good scientists.
Whatever happens with the reforms, Chacinska is "very optimistic," she says. "Right now, I've got really such great opportunities that everything basically is in my hands. So if something [doesn't] work out for me, I cannot blame anything, anybody, [and] not the country."
Elisabeth Pain is contributing editor for South Europe.