Six teams of scientists with wide-ranging expertise will come together to solve challenging problems with the support of new Howard Hughes Medical Institute Collaborative Innovation Awards (HCIA). HHMI will invest $40 million over the next four years to enable the teams to carry out potentially transformative research.
Together, the teams – each headed by an HHMI investigator -- include 28 researchers from 20 institutions in the United States, Germany, and Israel. Each collaborator will receive funds from HHMI to cover their research budget for the HCIA project, and the flexibility to pursue their best ideas.
“The most efficient way to tackle many of today’s biggest scientific problems is to bring together experts in a variety of fields. These teams have assembled the best people in the world to address challenging problems in creative ways,” said Jack E. Dixon, HHMI's vice president and chief scientific officer. “This award offers every member of the team the support they need to move that work forward.”
This is the second round of HHMI’s Collaborative Innovation Awards, which began in 2008 as a pilot program to encourage both HHMI investigators and scientists outside HHMI to undertake new projects of ambitious scope. “We want to enable researchers to take on challenging and important problems that really depend on a team effort,” says Philip Perlman, a senior scientific officer at HHMI who is overseeing the program. Without dedicated support, he added, such large-scale collaborations tend to proceed very slowly, if they happen at all.
The financial support and flexibility provided by the program enabled the eight teams that received awards in 2008 to tackle scientific problems such as surveying the effects of gene imprinting on the brain in mice and engineering a wireless sensor for monitoring intraocular pressure in patients with glaucoma. The success of that first round of awards convinced HHMI to continue the HCIA program.
HHMI investigator Peter Walter, a 2008 awardee who led a team investigating whether manipulating protein quality-control pathways could be beneficial for treating disease, says that project would not have been possible without an HHMI Collaborative Innovation Award. “This was not just dumping more money into something we were already doing. This was a huge collaboration which required lots of different expertise, and our award enabled us to assemble the team we needed,” he says.
Walter and his collaborators at the University of California, San Francisco and the Science for Life Foundation in Chile developed small molecules that alter the way cells detect and respond to unfolded proteins, and used them to reveal a potential drug target for treating multiple myeloma. “What my lab does best is establish mechanism,” he says. “Our collaborators brought in a strong cancer focus, and we were able to advance our work to a stage where industry is interested in pursuing it.” Walter will approach a similar problem from a new angle as a member of one of the team’s receiving a 2012 HCIA award, led by HHMI investigator Jonathan Weissman.
HHMI investigator Danny Reinberg, another 2008 award recipient, says his Collaborative Innovation team’s work on epigenetic influences on behavior has opened up an important new avenue of research in his lab. In 2008, Reinberg, a biochemist, recruited Shelley Berger, an expert on gene regulation at the University of Pennsylvania, and Jürgen Liebig, a leader in the study of insect societies from Arizona State University, to help him explore whether epigenetic regulation – changes that affect gene activity without altering DNA sequence—influences the stereotypical behavior of members of different social castes within ant societies.
Since then, Reinberg’s project team has determined the complete genome sequences of two species of ants and begun to establish ants as an experimental model for studies of epigenetics and behavior. “Thanks to the resources provided by the Collaborative Innovation Award, we’ve been able to do this very fast,” Reinberg says. Now, his team is poised to delve deeper into understanding the molecular mechanisms that act on the ant genome to elict caste-specific distinctions in behavior, morphology, and lifespan. With a new HCIA award, Reinberg has expanded his team and says he has “outstanding expectations” for continued progress.
In late 2011, HHMI investigators were again invited to propose plans for tackling challenging and potentially transformative research opportunities with teams of collaborators outside the HHMI community. The Institute received 71 HCIA applications, which were evaluated by panels of experts in three rounds of review.
The six teams selected will address a set of problems that includes determining the structure of challenging biological systems, mapping neural circuits in the brain, and investigating the role of spatial organization in certain biological functions. “These are well thought out teams of outstanding people,” Perlman says. “We expect bringing them together will create a synergy of expertise.”
The six new HCIA teams and their projects are:
Structures of challenging biological systems with the world’s first hard X-ray laser
Axel Brunger’s team will develop new methods of sample delivery, data collection, and analysis to enable structural studies of nanometer or micron-scaled crystals of biological molecules using the new Linac Coherent Light Source at the SLAC National Accelerator Laboratory in California.
Mapping global patterns of connectivity in the mammalian brain
Liqun Luo’s team plans to develop a suite of tools for mapping neuronal connections in the complete mouse brain, including those that extend across long distances, and use those tools to study the organization of neural circuits and how they are affected by specific neurotransmitters.
- Liqun Luo, HHMI Investigator, Stanford University
Live-cell proteomics of polarized cellular structures
Norbert Perrimon’s team will develop methods of isolating proteins located in spatially defined regions inside cells, which they will use to investigate the role of polarization in cellular processes, such as development and synaptic signaling.
Epigenetics of behavior, longevity, and social organization in ants
Danny Reinberg’s team will investigate how epigenetic regulation contributes to variation among individuals belonging to different social castes within ant societies.
- Danny Reinberg, HHMI Investigator, New York University School of Medicine
Polymerization and partitioning: mechanisms for regulating protein activity
Michael Rosen’s team will investigate how and why certain proteins are organized into dynamic, micron-scale clusters within the cell.
- Michael Rosen, HHMI Investigator, University of Texas Southwestern Medical Center at Dallas
A combined chemical and genetic approach to explore how chaperone and stress networks maintain the integrity of oncogene-addicted cancer cells
Jonathan Weissman’s team will characterize the network of proteins that responds to misfolded proteins within the cell, defining their interactions with one another and exploring their potential roles in initiating and sustaining cancer.