Durham, NC – Alejandro Aballay, PhD, Professor in the Department of Molecular Genetics and Microbiology and Director of the Center for Host Microbial Interactions at Duke University, will be receiving an NIH MERIT Award from NIGMS for his research project on the role of the nervous system in controlling immunity in the model host C. elegans.
Dr. Aballay’s project will be a multidisciplinary research program regarding the study of neural circuits involved in the control of stress responses and innate immunity. Recent studies from his laboratory indicate that different immune mechanisms are controlled at the organismal level by the nervous system. His laboratory has demonstrated that specific neurons suppress innate immunity in the intestinal cells of the nematode Caenorhabditis elegans, in part by down-modulating a mitogen-activated protein kinase signaling pathway similar to the mammalian p38 MAPK pathway that is highly conserved across metazoans. They found that NPR-1, a G-protein coupled receptor (GPCR) similar to mammalian neuropeptide Y receptors (NPYr), participates in a neural circuit that controls the p38/PMK-1 MAPK pathway. In addition, OCTR-1, which is an adrenergic GPCR for octopamine, also controls the p38/PMK-1 MAPK pathway and unfolded response (UPR) pathways that are expressed in non-neuronal tissues and that are necessary to alleviate the increased demand on protein folding during immune activation.
The studies are based on the general hypothesis that immune pathways are regulated at the cell-autonomous level and, by the nervous system, at the organismal level. They are taking advantage of the simple and well-studied nervous and immune systems of C. elegans to develop a whole-animal high-throughput system for chemical and genetic screens for novel immunomodulators and drugs capable of enhancing the imprinting of pathogen-induced aversive behaviors. Indeed, their more recent studies demonstrate that a dopaminergic neuronal circuit involving CEP/ASG neurons and the D1 dopamine receptor DOP-4 can be pharmacologically targeted to control the conserved p38 MAPK immune pathway. The identification of this neural circuit, and the demonstration that chemical inhibition of dopamine signaling in the nervous system can control immune pathways at the cell non-autonomous level, provides a proof of concept for the use of neural interventions to control infections and conditions that involve aberrant immune functions.
The objective of the MERIT Award is to provide long-term, stable support to investigators whose research competence and productivity are distinctly superior and who are likely to continue to perform in an outstanding manner. The provision of long-term stable support to such investigators is expected to foster their continued creativity and spare them the administrative burdens associated with preparation and submission of full-length research grant applications. This may allow investigators the opportunity to take greater risks, be more adventurous in their lines of inquiry, or take the time to develop new techniques. After the initial 5 years of support the MERIT awardee may request an extension of 3 to 5 more years based on an eight-page progress report and a one-page abstract of the research plan for the extension period. Alejandro just received the notice of grant award, and his first phase of five years of funding of the anticipated ten years of sustained support will commence soon.
Dr. Joe Heitman, MD, PhD, Chair of Molecular Genetics and Microbiology at Duke said, “Alejandro has been a stellar investigator at Duke for the past 15 years, and he joins a select cadre of Duke faculty who have received NIH MERIT awards.”
Only a select few Duke faculty have received this prestigious Merit Award including Dr. Marc Caron, James B. Duke Professor of Cell Biology; Dr. Loreena Beese, James B. Duke Professor of Biochemistry; Dr. Michael Krangel, Chair and Mary Bernheim Professor of Immunology; Dr. Blanche Capel, James B. Duke Professor of Cell Biology; Dr. Donald McDonnell, Chair and Glaxo-Wellcome Professor, Department of Pharmacology and Cancer Biology; Dr. Brigid Hogan, Chair and George Barth Geller Professor, Department of Cell Biology; Dr. Anna Mae Diehl, Florence McAlister Professor, Department of Medicine; Dr. Joseph Heitman, Chair and James B. Duke Professor of the Department of Molecular Genetics and Microbiology.
In addition, MERIT awards are given to research programs that have been continuously NIH supported for at least three cycles of funding, that have received a top score in their study section for two concurrent competitive renewals, and that have no revisions or amendments required. An investigator can usually only receive one in a lifetime, and only approximately 5% of NIH-funded investigators receive a MERIT award.