IGSP Funds 'Next-Gen' Sequencing Studies
September 30, 2008
CONTACT: Kendall Morgan
(919) 684-2850
kendall.morgan@duke.edu
Durham, NC -- In an initiative designed to catalyze the growth of genome analysis at Duke, the Duke Institute for Genome Sciences & Policy (IGSP) has announced a series of seed grants to use “next-generation” DNA sequencing technology for studies ranging from basic biology to clinical medicine. Four new projects will generate vast amounts of new sequence data to explore the biology of the human genome, symbiotic relationships between two species, bacteria found in the intestinal tract of newborn infants and diversity in the Costa Rican rainforest.
The pilot projects take advantage of some of the latest in DNA sequencing technologies, recently made available to all Duke researchers by the IGSP Sequencing Facility. Those instruments — capable of churning out terabytes of data at every run -- not only promise to speed the pace of genomic discoveries, but also to vastly expand the scope of scientific questions that can feasibly be addressed.
“The main goal of the IGSP is to promote good science across the campus,” said Greg Wray, head of the IGSP’s Center for Evolutionary Genomics and faculty director of the IGSP Sequencing Facility. “Now that we have these instruments, we want to lower the bar as much as possible, to help Duke researchers see what they can gain by using them.”
The IGSP-funded studies were chosen in part because of their potential to rapidly yield high-profile scientific publications and to attract new grant funding.
Led by Francois Lutzoni and Daniele Armaleo, both professors in the Department of Biology, the lichen project aims to sequence the two genomes of a “typical” lichen. While lichens appear to be a single entity, they actually represent a close association between a specialized fungus and a single-celled green alga, each with their own DNA. Lichens are considered among the most successful of all mutually beneficial, or symbiotic, partnerships between two species.
“Our project is the first to address the genetic and genomic adaptations that allow two distinct biological universes — a fungus and a eukaryotic alga — to interact and coevolve in intimate balance,” Armaleo said.
The new work builds on a long tradition of lichen study at Duke, dating back several decades. The researchers see this new partnership with the IGSP as a symbiotic arrangement all its own. “The merging of IGSP’s new resources with the Biology Department’s expertise in lichen biology creates a meta-symbiosis likely to catalyze dramatic advances here and elsewhere,” Armaleo said. The sequencing of lichen genomes had remained wishful thinking for years due to the steep economic and personnel investment typical of earlier technologies.
Already, the new work has yielded an exciting surprise: the first direct evidence that genes have been transferred between the lichen-forming fungus and its photosynthetic partner. The research team is now exploring that possibility in more detail.
A second pilot study led by Patrick Seed in the Department of Pediatrics will explore the bacteria that colonize the guts of extremely preterm infants born before 28 weeks gestation. Studies have shown that the makeup of the gut “microbiome” has important health consequences for human adults and animals.
Survival of extremely preterm infants has improved in the past decade, but the prevalence of health problems, including infection and poor growth, that may be linked to interactions between gut microbes and other factors continues essentially unchanged, Seed said. By taking a genomic approach to the study of those microbes in preterm infants, the researchers hope to uncover new ways to characterize patients in their care and to identify new targets for treatment or preventive strategies.
In the Costa Rican rainforest study, Wray and IGSP member Tom Mitchell-Olds, a professor in the Department of Biology, will use the next-generation sequencing tools to profile all of the active genes in the leaves and roots of some of the most dominant tree species there. The goal is to characterize those profiles under different conditions—during the wet and dry season and under different temperatures, for example—to shed light on how key species respond at the genomic level to stresses that are expected to become more prevalent as the earth warms. The project may be the first to apply these genomic tools to a non-commercial tree and to any tropical plant.
Finally, Professor of Pharmacology and Cancer Biology David MacAlpine’s study of the human DNA replication program will sequence the very earliest stretches of DNA that form as part of the process. The study aims to identify the locations in the human genome where DNA synthesis begins – so-called replication “origins” whose behavior is critical for maintaining the integrity of our genome and which are known to go awry in various cancers.
The projects now underway or in the planning stages highlight the versatility of the new sequencing technologies for genetic and epigenetic studies. In addition to DNA sequence, the new instruments can measure DNA replication, gene activity, chromatin composition and the chemical structure of DNA.
Wray also noted that the majority of people now capitalizing on the new facilities are researchers who had never operated such instruments before. “That’s a good sign, because we’re bringing something new to their research,” he said.
In addition to the pilot projects, plenty of other studies by IGSP researchers are already underway in the new facility, which IGSP Director Huntington Willard notes is rapidly becoming one of the busiest academic sequencing facilities in the country. “Our hope is that more and more investigators at Duke – both on the main campus and at the medical center – will see this approach as a new way to develop comprehensive datasets of information to address problems in biology and medicine that were not easily addressed before.”
To learn more about the new DNA sequencing instruments, the 454 Life Sciences Genome Sequencer FLX™ and the Illumina Genome Analyzer, see “Talkin ‘bout My Generation” in the April/May 08 issue of GenomeLIFE or visit the DNA Sequencing Core Facility.