In September, the National Institutes of Health (NIH) presented 50 New Innovator Awards to support creative investigators with innovative research ideas at an early stage of their careers. The program’s goal is to lower the barrier of preliminary data, which is required in the traditional NIH peer review, and support research that could have a high impact. To learn more about their progressive research, BioTechniques spoke with several of this year’s recipients in a series of profiles that will be published this week.
“Research and history shows that natural products are better source materials for developing antibiotic compounds. They’ve been shied away from, but it’s clear they hold the most power for developing new drugs,” says Carlson.
As an assistant professor of chemistry at Indiana University, Carlson’s research focuses on the identification of natural antibacterial agents and their effectiveness for drug-resistant infections. The goal is to develop drugs discovered in natural plants and microorganisms.
Currently, Carlson and graduate student Darci Trader are developing methods to isolate natural products. Traditional techniques extract and separate biological compounds based on characteristics such as size or charge, but Carlson’s team hopes to identify compounds in biological samples based on their functional group composition.
“We are working to develop new techniques for isolation and then strategies for trying to create even more effective drugs from natural products by conjugating or adding a number of structures to known drugs to try to amplify the activities the compound has,” says Carlson.
Specifically, they are targeting functional groups like the hydroxyl and the carboxylic acid in naturally-derived compounds. These hydroxyl functional groups are present in more than 70% of natural products and isolating them will be the first step toward the development of drugs from natural products. To isolate these compounds, Carlson’s team has created an enrichment tag based up a silyl-functionalized resin to enrich molecules based on their functional group composition (1).
But her research has only reached technology development stage. Her group has not found or identified natural compounds with antibiotic properties yet.
“We are currently testing our enriched natural product fractions against Escherichia coli, MRSA, MSSA, and Mycobacterium smegmatis, a non-pathogenic model organism for Mycobacterium tuberculosis,” says Trader.
In the six years since she received her Ph.D. from the University of Wisconsin, Carlson’s career has been supported by several organizations. In 2005, she received an American Cancer Society Postdoctoral Fellowship. In 2007, Carlson received an NIH Pathway to Independence Award. Last year, the Pew Charitable Trusts named her a Pew Scholar. And now, she has received the 2011 NIH New Innovator Award.
“I am not surprised in the least by her success so far as a faculty member at Indiana,” says Benjamin Cravatt, a professor at the Skaggs Institute for Chemical Biology who mentored Carlson. “In a very short time, she has established an innovative research program that addresses a very challenging scientific problem, namely, the functional enrichment and characterization of low-abundance, bioactive natural products.”
Furthermore, Carlson’s group hopes that some of these new natural products will target different pathways in bacteria that cause infectious disease. Current drugs only attack a limited numbers of pathways, and bacteria readily develop some resistance to these drugs.
“A major challenge is that drug discovery is very complex and a lot of it is based on serendipity, whether or not you find the compounds that give the appropriate activities you’re interested in. Our strategy is develop techniques that allow us to use both known compounds and unknown compounds and decrease the risk by screening for some properties that we know should be advantageous while at the same time discovering new, more effective activities,” Carlson says.
(1) Odendaal, A.Y., D.J. Trader, and E.E. Carlson. 2011. Chemoselective enrichment for natural products discovery. Chem. Sci. 2011, 2:760-764