UA Parkinson’s Researcher Joins ‘Scientific Dream Team’ Through HHMI Collaborative Innovation Awards

Surprising—sometimes groundbreaking—findings can emerge when scientists follow ideas that stray from the primary path of their research. But these promising detours may prove challenging to pursue for scientists who need to marshal time, expertise, and resources in a constrained funding environment that favors more predictable research proposals.

A $40 million pilot program from the Howard Hughes Medical Institute will now enable eight teams of scientists, including one team involving a University of Alabama Parkinson’s disease researcher, to devote substantial time and energy pursuing collaborative, potentially transformative research.

“We’re excited about this program because of the quality of the projects, but also because it broadens the community of scientists supported by HHMI,” said Thomas R. Cech, president of HHMI. “It incorporates people outside of the HHMI investigator program in solving important problems, and lets us do something really new.”

Eight teams of three to six scientists, each headed by an HHMI investigator, will bring together their diverse expertise to explore a wide range of potentially transformative research areas. These include development of an ultraminiature implantable wireless sensor for monitoring progression of glaucoma; the identification of drugs capable of clearing toxic brain proteins that cause neurodegenerative diseases; and determining whether the study of gene regulation in ants can be used as a model for human aging.

Dr. Guy Caldwell, associate professor of biological sciences at The University of Alabama, is part of a five-person team led by Dr. Susan Lindquist, a Howard Hughes Medical Institute investigator. This HHMI-supported team’s goal is to discover new strategies to target the biological mechanisms that break down in Parkinson’s disease and other neurodegenerative disorders.

“The idea behind our project is to transition to a new era in medicine,” said Lindquist, who is also a member of the Whitehead Institute for Biomedical Research.

The team, which an HHMI news release refers to as “a sort of scientific dream team,” has developed an action plan that will exploit the powerful tools available to study gene function in three different model organisms (yeast, worms, which Caldwell uses in his research, and mice) and integrate genetic data from large-scale studies of people who have Parkinson’s disease. The plan also calls for using new stem cell technology to generate cellular and animal models that can be used in screening for new drug therapies to treat neurodegenerative diseases.

In addition to Lindquist and Caldwell, members of the team include Rudolf Jaenisch, a stem cell and cloning pioneer who is also at the Whitehead, Richard Myers, who studies the genetics of Parkinson’s disease at Boston University School of Public Health, and Jean-Christophe Rochet of Purdue University, whose research probes how the buildup of misfolded proteins damages nerve cells.

Researchers in UA’s Caldwell Lab have developed the microscopic worm, C. elegans, as an animal model for studying human neurological diseases. The worms share many traits, including dopamine producing neurons, with humans to make them widely accepted models for studying human disease. Three independent Nobel Prizes this decade have been awarded to worm researchers. In humans with Parkinson’s disease, the neurons in the brain which normally synthesize dopamine malfunction and degenerate over the course of aging.

Using the transparent worms, the UA researchers can trace both the pathways of the worm’s dopamine neurons and investigate their internal protein functions. Caldwell’s group previously took a human Parkinson’s gene and transplanted it into the worms, along with a fluorescent jellyfish protein, both of which are “turned on” by neurons that produce dopamine.

“We can use the fluorescent protein as a light bulb for seeing if the dopamine neurons are alive,” Caldwell said. “If the light goes out, they are dying.” Finding ways to keep the light on in the worms can provide clues for potential treatments.

“What excites me most about this HHMI collaboration is that, unlike most research on drug discovery that is aimed at halting progression of PD, this project actually has the potential to cure the disease,” Caldwell said. “That is simply thrilling.”

The eight projects were selected from among 62 proposals submitted by HHMI investigators and will bring together a total of 33 researchers from 16 institutions in the United States and Chile. The Institute will evaluate the success of the eight projects selected in this pilot phase, and expects to expand the program in coming years.

“This program allows scientists to attack problems that one person can’t solve,” said Jack Dixon, HHMI’s vice president and chief scientific officer.

Philip Perlman, a senior scientific officer at HHMI who is overseeing the program, said HHMI developed the Collaborative Innovation Awards because it recognized there was a need for a creative funding mechanism to support these large-scale collaborations. “Many research groups can find it difficult to allocate the resources to allow one or more members to devote years to a project that could yield important results, but may never directly further the lab’s own mission.”

The financial support offered by the Collaborative Innovation Awards has enabled the lead investigators to assemble teams of scientists with the knowledge and skills necessary to explore the important questions that pique their scientific curiosity – and to assure that the funding is available to see those projects through for up to four years. Each collaborator will receive funds from HHMI to cover their research budget, including the purchase of new equipment if needed.