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HHMI’s International Early-Career Scientists

Earlier this week, the U.S.-based Howard Hughes Medical Institute (HHMI) announced the first group of recipients of its International Early Career Scientist (IECS) awards. The program aims to help early-career scientists build successful labs in less well-off countries, and to promote strong ties between international scientists and HHMI Investigators.

The 28 early-career scientists were selected from 760 applications. The majority of the awardees are located in China, Portugal, and Spain, but winners are also based in South Africa, Italy, Argentina, Brazil, Chile, Hungary, India, Poland, and South Korea. What the IECS awardees share is that they all are leading biomedical scientists, spent time training in the United States, and established their own labs within the past 7 years.

The awardees will be integrated into HHMI’s scientific community and will each receive $100,000 a year for 5 years to run their labs, and another $150,000 in the first year to buy major equipment. More information about the program can be found in this ScienceInsider post by Jocelyn Kaiser.

Science Careers talked to three awardees -- from China, Spain, and Portugal -- about their careers, past, present, and future.

Xiaochen Wang, China

Xiaochen Wang

Xiaochen Wang

CREDIT: Kevin Wolf/AP, © HHMI

Xiaochen Wang, 43, grew up on the campus of Peking University where both her parents are computer scientists. This early exposure nudged her toward a research career, Wang says, but she wanted to enter a field that her parents “do not know very much about.” She obtained a B.Sc. degree with a major in microbiology from Shandong University in 1992.

Wang then entered a doctoral program in genetics at Peking University, doing her research work at the National Laboratory of Protein Engineering and Plant Genetic Engineering with Zhangliang Chen as her mentor. Wang purified an antifungal protein from the orchid Gastrodia elata and characterized it so that it could be used, potentially, to create transgenic plants that are resistant to fungal infection. In the last year of her doctoral program, she went to work at Ghent University in Belgium where she was exposed to a more international research environment, learned about a broad range of ideas and techniques, and for the first time had timely access to international journals. “I benefited a lot,” she says.

While doing her Ph.D., Wang came across a defense mechanism in plants involving apoptosis, where “the plant cell is induced to die around the infection site so the pathogen cannot be spread to other tissues,” Wang says. Her interest was piqued: Upon graduating in 1999 she joined the lab of Ding Xue at the University of Colorado, Boulder, to study how cell death is regulated in the model organism Caenorhabditis elegans.

In the Xue lab, Wang changed tracks once more upon discovering that the apoptosis-inducing factor she was studying had another function: to help dying cells degrade their DNA and mark themselves as trash to be cleared. She refocused her work on how those dying cells are recognized and engulfed by clean-up cells called phagocytes.

Wang returned to China in 2006 with a 5-year assistant investigator position at the National Institute of Biological Sciences (NIBS) in Beijing. At the time, a handful of genes were known to be involved in the engulfment of apoptotic cells but these were not sufficient to explain the whole process. Wang designed genetic screens that allowed her to find several new genes involved in engulfment. Her lab was also among the first to identify genes involved in the phagocytic digestion of cell corpses. “How corpse clearance is regulated … is not understood very well,” Wang says. But this process is important because “if the apoptotic cells are not properly cleared … it will affect the cell death activation” in organisms like worms and cause persistent inflammation and autoimmune responses in humans.

Launched in 2003 with government support, NIBS offers its group leaders generous funding for the duration of their 5-year contracts. “Investigators in this institute do not have to apply for grants themselves, so … you have all your time to focus on doing your own science,” she says. “My lab is well equipped and we can access … very good core facilities at NIBS,” she adds. On average, she has around 15 students working for her at a time. Last year, she passed her evaluation, her 5-year contract was renewed, and she was promoted to Associate Investigator. NIBS does not offer tenure.

Wang expects her HHMI award to have a great impact on her career. “One thing is the recognition,” she says. Another is “the opportunity to get connected with many, many great scientists.” Communicating and collaborating with international scientists “is still something that’s very much lacking in China,” she says.

José García-Pérez, Spain

Jose García-Pérez

Jose García-Pérez

CREDIT: Kevin Wolf/AP, © HHMI

José García-Pérez, 37, remembers the day he was given a chemistry kit to play with; he was about 11. The set inspired his curiosity about how things work. Later, as a high school student, he developed a special fondness for biology.

García-Pérez earned his B.Sc. degree in pharmaceutical chemistry from the University of Granada in 1997. For his Ph.D., he joined the lab of Manuel Carlos López López in the Department of Molecular Biology at the López-Neyra Parasitology and Biomedicine Institute, also in Granada. At first he worked on a vaccine against Chagas disease, but then he noticed some recent findings made by other researchers in the lab.

Chagas disease is caused by the parasite Trypanosoma cruzi, which, in different forms, infects both humans and insects. Insects act as a vector for the disease. When comparing the two parasitic forms in an effort to discover a vaccine target, the researchers found that much of the difference arose from the expression of a peculiar genetic sequence known as a retrotransposon. These highly repeated bits of DNA are capable of expressing and inserting new copies of themselves back into the genome -- hence the sobriquet “jumping genes.” “I fell in love with the idea of a dynamic genome,” García-Pérez recalls. So, 2 months into his Ph.D., he switched his project and started analyzing the presence and functions of retrotransposons in the trypanosome. The goal was to elucidate the molecular mechanisms underpinning retrotransposons’ uncanny genomic mobility.

In retrospect, García-Pérez says, the move seems risky. Because of its atypical gene regulation, the trypanosome “didn’t allow me to do much genetic manipulation,” he says. In 2003, during a postdoc with John Moran in the Human Genetics Department at the University of Michigan Medical School in Ann Arbor, he set out to develop a new model. Using human pluripotent cells, García-Pérez tried to get a retrotransposon called LINE-1 to jump around in the genome. His breakthrough came when, after hearing a talk about epigenetic markers -- chemical modifications that affect gene expression -- he tried to block epigenetic mechanisms in his assays on the chance that these might be underlying his failure to induce the retrotransposon's expression and mobility. He didn't just get his model to work the same day; he also demonstrated that LINE-1 expression is epigenetically silenced in pluripotent cells.

In June 2008, García-Pérez took a group leader position in molecular embryology, stem cells, and cancer at the University of Granada’s Centre for Biomedical Research, where he launched his own research on LINE-1 biology. Last June, he switched to the Department of Human DNA Variability at the Centre for Genomic and Oncological Research in Granada. Since coming back to Spain, he has continued to collaborate with Moran, going to Michigan as a visiting researcher every year and sharing projects and students.

Currently, four postdocs, three Ph.D. students, and one technician work in García-Pérez's lab. Last year, in spite of widespread national budget cuts, he was able to renew his research grant for another 3 years. He expects the extra funding from HHMI to give him “the sensation of freedom in research,” he says. Now people working in his lab will "have the opportunity to … just [be] curious.” He plans to do genomewide analysis to identify new genes with a role in the epigenetic control of LINE-1 mobility, and to go looking for more cell types where LINE-1 mobility occurs. “I am looking forward to having the 5 years of good funding and being able to focus on science.”

Miguel Godinho Ferreira, Portugal

Miguel Godinho Ferreira

Miguel Godinho Ferreira

CREDIT: Kevin Wolf/AP, © HHMI

Miguel Godinho Ferreira’s scientific career was largely inspired by his father, who taught him to be curious about how the world works. “The other thing that I owe to him is the idea [to] go and look for the answers yourself,” he says.

Godinho Ferreira, 41, obtained a 5-year degree in biology from the University of Lisbon in 1993. He spent his last year as a Lisbon student studying cell-cycle regulation in yeast at the University of Manchester in the United Kingdom, with an Erasmus scholarship from the European Commission. Back in Portugal, he entered a Ph.D. program in biology and medicine run by the Gulbenkian Institute for Science (IGC) in Oeiras. The new program was unusual in that its students attended lectures given by visiting researchers during their first year and then were sent abroad to do their doctoral research. Every year, they met back in Portugal to hear about each other’s work. This early exposure to a wide range of research made Godinho Ferreira the broad-thinking scientist he is today, he says. It also “created a group spirit which we trust and rely on” still.

Godinho Ferreira did his Ph.D. at the Imperial Cancer Research Fund's Clare Hall Labs near London under the supervision of John Diffley. (The fund is now called Cancer Research UK.) There, he studied the regulation of DNA replication in budding yeasts during the cell cycle.

By the time he graduated from University College London in 1999, Godinho Ferreira had grown tired of studying replication because the field had reached the point where "people would just repeat each others’ experiments,” he says. So he began to study telomere biology using fission yeast during a postdoc with Julie Cooper, first at the former University of Colorado Health Sciences Center in Denver and, 3 years later, at Cancer Research UK’s Lincoln’s Inn Fields labs in London.

Telomeres are repetitive stretches of DNA that cap natural chromosome ends to protect them from being damaged or fused together during DNA replication. In Cooper’s lab, Godinho Ferreira worked to understand why telomeres function differently than deleterious chromosome ends generated by the abnormal breaking of chromosomes. Abnormal chromosome ends can stimulate DNA repair mechanisms and trigger cell death, while one of the roles telomeres play is to ensure a normal cell cycle. Godinho Ferreira helped show how some telomere-associated proteins maintain telomeres and play a role in their regulation of the cell cycle.

Returning to Portugal in 2006, Godinho Ferreira joined IGC, where he has been leading the Telomere and Genome Stability Laboratory. Funding obtained from the Association for International Cancer Research allowed him to get started, hiring a postdoc and a student and buying supplies for 3 years. More recently, Godinho Ferreira, who now employs three Ph.D. students and four postdocs, has been working to establish Zebrafish as a new model system to try and understand the role of telomeres in aging and the role of telomere-elongation enzymes in cancer. His group employs both the bottom-up, molecular biology approach and the top-down, organism approach, hoping that by “having two ways of thinking in the lab and allowing people to share thoughts and projects, … we could probably be an excellent lab and try to integrate the whole spectrum,” he says.

Godinho Ferreira sees the HHMI award as an important vote of confidence. “One of the things [about] being in Portugal is that there are very few of us doing things in our field,” which makes it difficult to get feedback, he says. “This is a fragile time in my career. I’m changing organism. I’m embarking on a new type of thinking." He sees the HHMI award as a message that he's "on the right track."

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