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Molecular structure
Three Allen Distinguished Investigator projects focus on epigenetics, or how genes are turned on and off. Researchers will study how the 3-D shape of the genome and the presence of regulatory molecules impact the behavior of cells.(Molekuul.be via Paul G. Allen Frontiers Group)

Epigenetics, aging and microbial evolution: Those are the latest words in biomedical research for the Paul G. Allen Frontiers Group, backed up with $7.5 million in awards for five teams of scientists.

Each of the teams will receive $1.5 million over the next three years to boost early-stage studies that have the potential to yield medical breakthroughs.

“It’s part of Paul Allen’s growing commitment to the idea that this is the century of bioscience,” Tom Skalak, executive director of the Seattle-based Frontiers Group, told GeekWire. Allen, one of the founders of Microsoft, launched the Frontiers Group last year with a $100 million commitment.

Previous beneficiaries of the program include Berkeley’s Jennifer Doudna, one of the pioneers of the CRISPR-Cas9 gene editing technique; and MIT’s James Collins, who’s using synthetic biology to counter infections such as MRSA.

Just this month, researchers who are supported by the Frontiers Group published provocative research about two-headed flatworm regeneration on the International Space Station.

Three of the newly announced awards focus on epigenetics, the study of how environmental factors influence gene expression. “Epigenetics is how DNA and our genome is controlled,” Skalak explained.

He compared the molecular mechanisms behind epigenetics to the control knobs on an old-fashioned amplifier. “What if you could dial up four or six genes by 20 percent, 40 percent, 80 percent?” Skalak said.

The work supported by the Frontiers Group could identify control points linked to types of cancer, neurodegenerative diseases such as Alzheimer’s or other maladies that are thought to be influenced by genetics as well as environment and lifestyle.

One of the $1.5 million awards will support research into ways to measure the progress of the aging process. Another award will focus on microbial evolution and the worrying rise of antibiotic resistance.

Skalak said the Frontiers Group is designed to support 20 to 30 researchers at a time, filling out a biomedical portfolio that extends from “the molecular scale all the way up to phenomena that might be modeled on the organ scale.”

He acknowledged that his job is a bit like that of a baseball scout trying to build a balanced team, but with one big difference: “In baseball, the field stays the same size,” Skalak said. “In science, the field is always moving.”

Here are the new players in the Frontier Group’s lineup:

  • Fei Chen of the Broad Institute, and Jason Buenrostro of the Broad Institute and Harvard: Chen and Buenrostro aim to visualize the architecture of the genome, and sequence individual regulatory elements within cells. This capability will enable researchers to understand how spatial organization of the genome is regulated, and study how epigenetic changes affect normal and diseased cells.
  • Jan Ellenberg of the European Molecular Biology Laboratory, and Ralf Jungmann of the Max Planck Institute of Biochemistry and LMU Munich: Ellenberg and Jungmann are developing a novel technology that uses barcoded fluorescent proteins to “paint” DNA sequences with specific epigenetic markers, and super-resolution microscopy to visualize those painted sequences at the level of single genes. Using this tool, they plan to map the complete 3-D architecture of the epigenome in single human cells, and analyze how the structure changes as genes are turned on and off.
  • Charles Gersbach of Duke University: Gersbach is working on techniques to induce any epigenetic state in any cell type or tissue. The first application would be to generate a variety of neurons to study drug response, disease and the impact of epigenetic regulation on learning and memory.
  • Steve Horvath of UCLA: Because aging is a leading risk factor for multiple chronic diseases, finding a way to slow biological aging could offer a powerful medical tool. Horvath has recently developed a way to measure the age of any human tissue by looking at a combination of chemical changes to the DNA. This “epigenetic clock” is highly correlated with chronological age and even predicts life expectancy. Horvath will seek to enhance the clock so that it becomes a universal measure of aging across different species. Such a clock could point to strategies for slowing the aging process.
  • Rachel Whitaker of the University of Illinois: Researchers have identified regions of the genome that can move rapidly between cells, creating dramatic and unpredictable genetic changes. Infectious bacteria take advantage of these mobile genetic elements, or MGEs, to evade antibiotics through rapid evolution. Whitaker’s project will create models of MGEs and their evolutionary roles within a human system, and fine-tune those models to get a better handle on this crucial evolutionary process.
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