Duke University Medical Center researchers have discovered a genetic link between the nervous system and the immune system in the well-studied worm, C. elegans, and the findings could illuminate new approaches to human therapies.
For some time, scientists have theorized a direct link between the nervous and immune systems, such as stress messages that override the protective effects of antibodies, but the exact connection was unknown. During this week’s podcast, Dr. Alejandro Aballay points out that this is the first time that a genetic approach has been used to demonstrate that specific neurons in the nervous system are capable of regulating the immune response in distant cells. The Duke study was published in the Sept. 18 issue of Science.
After talking about the benefits of working with C. elegans as a model oganism, Dr. Aballay explains that in addition to shedding light on the neuronal regulation of immunity, the results of the Duke study can also lead to a better understanding of non-neuronal processes such as fat storage and longevity. He also discusses what the scientific team has in mind to advance this research.
Alejandro Aballay earned his bachelor's degree in Pharmacy from Juan A. Maza University, in Mendoza, Argentina, in 1994. During this time, he worked as an undergraduate student at Nacional de Cuyo University, in Mendoza, Argentina, where he studied soil bioremediation. He finished his M.S. equivalent studies in 1995 and started exploring the machinery that governs early steps in endocytosis at Nacional de Cuyo University. During this period, he received a World Bank fellowship to complement his studies in endocytosis by working as a summer student for two consecutive years at Washington University, in St. Louis, Missouri. In 1998, he earned his Ph.D. at Nacional de Cuyo University and received a Pew Fellowship to move to St. Louis, where he continued his studies in endocytosis at Washington University. In 1999, following an interest in bacterial pathogenesis he developed while studying the intracellular transport of Brucella abortus when he was a graduate student, he moved to Boston to join the Ausubel laboratory at Harvard Medical School. Dr. Aballay moved to Durham in 2002 to join the Department of Molecular Genetics and Microbiology, where his studies focus on what makes bacteria pathogenic and hosts resistant.
In the Ausubel laboratory, Dr. Aballay developed a novel pathogenesis system utilizing the simple well-studied nematode Caenorhabditis elegans and the common human bacterial pathogen Salmonella enterica. Salmonella is well known for its ability to cause food poisoning. Nematodes like C. elegans eat bacteria and surprisingly, C. elegans is killed when it is provided S. enterica as a food source. This killing is accompanied by a persistent infection of S. enterica in the C. elegans intestine. Importantly, Dr. Aballay has shown that several well-studied S. enterica virulence factors required for causing disease in mammalian hosts are also required for C. elegans killing. This validates the use of C. elegans as a host to model Salmonella infection in mammals, including humans.
Dr. Aballay's laboratory takes advantage of the compromise between complexity and tractability of the C. elegans-S. enterica pathogenesis model. The focus of the laboratory is to use C. elegans as a host to screen thousands of bacterial clones from mutagenized libraries to identify novel Salmonella virulence factors and to address how they alter host signaling pathways. Since several components of innate immunity are conserved among different organisms throughout evolution, his group is also exploiting the genetic and genomic resources available for C. elegans to study the basis of the immune response.
Dr. Aballay is a recipient of the 2005 ICAAC Young Investigator Award. Dr. Aballay also serves as an editor for the journal PLoS One, a new open access journal from the Public Library of Science.