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Hot topics in chemical biology and drug development at EB2011

Thu, 04/07/2011 - 10:39am
EurekAlert

WASHINGTON, April 7, 2011 What do blinking fireflies, the cellular power plants that are human mitochondria, parasitic worms in sub-Saharan Africa and synthetic sugars have in common? At first glance, not a lot; but, after a good hard look, they represent bright threads in the tapestry of knowledge for those trying to patch the gaps between chemical biology, technology, therapies and cures.

In the coming days, as part of the Experimental Biology 2011 conference in Washington, D.C., two dozen researchers will go public about their ongoing work aimed at improving our understanding of biological systems and contributing to our cache of healing compounds.

Additionally, at the special four-day program sponsored by the American Society for Biochemistry and Molecular Biology, the work of 12 scientists who are making some of the hottest advances in technology and drug discovery will be showcased.

The dozen 25-minute talks and 12 other shorter presentations will be given in Room 207B of the Walter E. Washington Convention Center.

"We have a fantastic lineup of speakers who will address many different aspects of chemical biology and drug development," said organizer Shana O. Kelley. "We will hear from scientists developing powerful tools for cellular analysis, as well as those who study the molecules that cause disease and the development of new molecules that can treat disease."

The program will be divided into the following four themes:

The Chemical Biologist's Toolbox

The first session, to be held from 9:55 a.m. to 12:10 p.m. Sunday, will highlight new tools being used to reveal the chemical details of biological phenomena. These tools allow researchers to approach biological problems from new perspectives, often at a molecular level, and inside living organisms.

A team of collaborators from Lawrence Berkeley National Laboratory and the University of California, Berkeley, has developed a biological probe based on luciferase, the enzyme that lights fireflies. The probe monitors hydrogen peroxide in mice noninvasively, allowing researchers to track infectious disease and cancer without harming the study animals or even shaving their fur.

A Wayne State University team is working to determine the spatial distribution of disease-specific proteins in tissue. They have developed a new method for imaging and simultaneous identification of biological compounds. According to researcher Sarah Trimpin, the team can directly identify proteins in mouse brain sections that are unique to a given region within < 0.001 of an inch. "This new mass-spectrometric technology is fast and will help researchers better understand the boundaries of diseased tissue," she explained.

Trimpin said she hopes it will accelerate researchers' understanding of the molecular basis of diseases such as cancer metastasis.

Meanwhile, a group at Washington University is developing new technologies to further probe protein structure under biological conditions.

"The high-resolution protein structures that you see on Wikipedia have been obtained by X-ray crystallography and nuclear magnetic resonance -- and these are important reference points for understanding proteins in biology," explains Michael L. Gross. However, he said, proteins don't do their jobs in isolation. "Rather, they work in complex biological media of cells in the presence of many other proteins and substances."

Gross and his team are pursuing mass-spectrometry-based methods to better understand protein function, folding and unfolding, and interactions in such complex states.

Peptide-Based Drug Delivery, Drug Discovery and Biomaterials

The second session, which will be held from 3:45 p.m. to 6 p.m. Monday, will highlight recent advances in the use of peptides as potential drugs and biological probes.

One research team, based at the University of Toronto and led by event organizer Kelley, has been working on delivering drugs to mitochondria, which provide cells with energy they need to move, divide, produce metabolites, contract and so forth.

"The mitochondria are the powerhouses of the cell and are often dysregulated in diseases like cancer," explains Kelley. "They have evolved to be difficult to penetrate, because energy production requires a tightly regulated barrier that allows only ion transport."

The challenge of mitochondrial targeting recently was overcome by Kelley's team's discovery of cell-permeable, engineered mitochondria-penetrating peptides. "Recently, we have harnessed these carriers for drug delivery and have discovered that their use presents unique advantages in circumventing drug resistance in cancer cells," Kelley said.

Because the team can hide drugs in the mitochondria of cells, the mechanisms that cells typically use to deactivate drugs don't work, Kelley explained, "and the fact that the mitochondria are difficult to penetrate prevents cells from devising a quick solutions to counteract the toxicity of chemotherapeutics."

Novel Approaches to High-Throughput Drug Discovery

The third session, which will be held from 9:55 a.m. to 12:10 p.m. Tuesday, will focus on high-throughput methods for drug discovery and understanding disease progression. High-throughput screening allows for the automation of millions of biochemical, genetic or pharmacological tests through the use of robotics, software, and sample handling and detection devices.

Among the speakers for this session is Michelle Arkin of the University of California, San Francisco, whose work focuses on often-neglected tropical diseases that primarily affect the very poor in developing countries.

Schistosomiasis, one of the diseases Arkin's team is studying, is caused by parasitic worms and is acquired through contact with contaminated water. "It infects at least 200 million people, particularly children, in sub-Saharan Africa and parts of Asia and South America," Arkin said, but using high-throughput robotics and imaging technologies allows for the characterization of how drugs work and testing many more compounds than was previously possible.

"Applying high-throughput technology to this and other parasitic diseases will eventually improve drug options for patients, Arkin said. "Furthermore, applying the team's tools to new diseases pushes the technology in new directions."

The Chemical Biology of Human Disease

The fourth and final session, to be held from 1:45 p.m. to 4 p.m. Wednesday, will look at the merging of chemistry and biology to better understand disease states at a molecular level and to advance the development of novel therapeutics.

Among the presenters will be Peter H. Seeberger, a researcher at the Max Planck Institute in Germany, whose team is creating synthetic sugars as a means to fight disease in the developing world.

"I will speak about the use of synthetic sugars made using an automated synthesizer to find the malaria toxin that kills about 2 million children per year," Seeberger said. "This synthetic sugar is the basis for an anti-toxin malaria vaccine candidate we are currently developing."

A research team at Wayne State University led by event organizer Hendrickson is looking at a common lipid modification of proteins called GPI membrane anchoring, a process that is upregulated in many types of cancer.

"The enzyme that attaches these glycolipids to proteins is perhaps the last major protein modification enzyme that remains poorly understood," Hendrickson noted. "This dearth in knowledge is because it is membrane-associated, and there is not a robust high-throughput (test) to facilitate its characterization."

Hendrickson's research group is developing a test for this enzyme and also is evaluating how it assembles. She said she hopes that her work will eventually lead to a detailed understanding of the role of the enzyme, called GPI transamidase, in cancer.

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