Harvard University - Department of Molecular & Cellular Biology


by Cathryn Delude

May 9th, 2013

The prestigious Howard Hughes Medical Institute (HHMI) has appointed Hopi Hoekstra as an HHMI Investigator. The Alexander Agassiz Professor of Zoology and Curator of Mammals in the Museum of Comparative Zoology, Hoekstra holds joint appointment in the Departments of Molecular and Cellular Biology (MCB) and Organismic and Evolutionary Biology (OEB). She studies wild mice both in the field and in the laboratory to discover the molecular basis of how adaptation to novel selective pressures generates and maintains diversity in nature. Her goal is to understand the entire adaptive process, from the molecular details to the organismal responses.

"This is a very exciting time for my lab,” says Hoekstra, also the Curator of Mammals at the Museum of Comparative Zoology. “The HHMI appointment will allow us to pursue more creative and risky projects and ones that may take longer to come to fruition than a typical grant cycle."

HHMI funds individual researchers rather than projects, as most grants do. Selected for their demonstrated creativity and productivity, HHMI investigators receive generous funding over five-years, with potential renewal. The long-term, flexible funding gives investigators the freedom to explore and even change direction in their research.  Hoekstra welcomes this flexibility because her work crosses traditional disciplinary boundaries, which can make it challenging to secure more traditional grants.

Hoekstra’s Quest: The Genetics of Adaptive Evolution

Early in her career, Hoekstra made a splash by studying the common deer mice both in their natural setting and in the lab to track the molecular, genetic and developmental basis of evolutionary change in traits that affect fitness of organisms in the wild. She developed a creative and powerful multi-disciplinary “forward genetics” approach for identifying the precise genes affecting morphological traits during adaptive evolution. To understand how tiny changes in DNA lead to sometimes dramatic changes in phenotype, she integrates cell and molecular biology, ecology, behavior, genomics, evolutionary theory, and computational biology.

Hoekstra originally focused on physical traits, asking such questions as how many genes and what types of DNA mutations does it take for a brown mouse to become blonde after it colonizes a region of sandy beaches? Her work on the lava-dwelling populations of rock pocket mice was one of the first examples of a specific gene influencing a trait affected by natural selection. In addition to looking at pigmentation, her lab studied skeletal development and reproduction, specifically sperm morphology and behavior.

Her lab is now expanding her approach to find the genetic basis for the behavioral diversity of natural populations of mammals, for example dramatic differences in burrowing behavior as well as exploratory and social behavior.

Some of the variation Hoekstra and others observe in animal behavior is controlled by genes, but behavior is hard to measure, so it has been very difficult to isolate such genes, much less to learn how they evolve to adapt to new environmental conditions. So Hoekstra first took advantage of what Richard Dawkins called “extended phenotypes,” animal architecture such as bird nests, beehives and mouse burrows. “Artifacts are easier to measure than behavior, but we can treat the length of a mouse burrow just like the length of the limb,” says Hoekstra. “We measure the morphological output of behavior.” This work has lead to the discovery of specific gene regions associated with burrow differences, which she believes is linked to motivational differences in these mice.

By discovering genes that contribute to variation in natural populations of mice, whether physical or behavioral traits, she hopes to shed some light on the genetics of human variation.  “These variants we discover occur in wild mice and that means, by definition they don’t have large adverse effects on their survival or reproduction. Therefore they may be common in other species, like humans.” By studying burrowing in mice, for example, she may be able to learn about motivational differences in other organisms.

Hoekstra Bio

Hoekstra received her B.A. in Integrative Biology from UC Berkeley, and she completed her Ph.D. in 2000 as a Howard Hughes Predoctoral Fellow at the University of Washington. She first became interested in adaptation as a NIH Postdoctoral Fellow at the University of Arizona. In 2003, she became an Assistant Professor at UC San Diego, and started her work on deer mice. Three years later, she moved to Harvard University, where in addition to her dual appointments in the MCB and OEB departments, she is the Curator of Mammals at the Museum of Comparative Zoology.

More About The HHMI Investigator Program

The HHMI Investigator program urges its researchers to take risks, to explore unproven avenues, and to embrace the unknown—even if it means uncertainty or the chance of failure. HHMI investigators have made many important research advances—from the discovery of genes related to cystic fibrosis, obesity, high blood pressure, colon cancer, and other diseases to insights about memory, vision, and olfaction. In 2012, there were 330 Howard Hughes Medical Institute investigators, including 15 Nobel laureates and 157 members of the National Academy of Sciences.

During periodic, open competitions, HHMI solicits applications from researchers at universities, medical schools, and other research institutions across the United States, with the aim of identifying individuals who have the potential to make significant contributions to science. Once selected, HHMI Investigators continue at their “host institutions,” typically leading a research group of 10–25 students, postdoctoral associates, and technicians. The appointment can be renewed after an exacting review process.

Read more in HHMI's press release

View Hopi Hoekstra's Faculty Profile