November 3, 2011

Aliquots — research highlights from VUMC laboratories

Glowing brain (iStock)


Extreme makeover: neuron edition

Neuronal circuitry is an ongoing remodeling project. Developmental signals and experience initiate processes that remove existing connections (synapses) and build new connections at alternate sites. This synaptic plasticity is crucial to the development and maintenance of the nervous system and to learning and memory, but the genes that contribute to synaptic remodeling are largely undefined.

David Miller, Ph.D., and colleagues studied the relocation of certain synapses in developing C. elegans worms to identify molecular components of synaptic remodeling. They identified 19 remodeling genes – conserved between worms and humans – that encode a diverse set of protein types. They demonstrated that one of these genes, IRX-1, functions as a key regulator of remodeling and that it works in a common pathway with a previously identified factor, UNC-55.

The synaptic remodeling genes they report in the Oct. 26 Journal of Neuroscience will be useful for future studies aimed at elucidating the molecular mechanisms of synaptic plasticity.

This research was supported by grants from the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke and the National Institute of General Medical Sciences.

Leigh MacMillan


Let there be light and melatonin

Joshua Gamse, Ph.D., and colleagues examined the effects of light and melatonin – a hormone secreted during the dark phase – on development of the habenular nuclei, brain regions involved in functions ranging from aversive learning to reproduction, in zebrafish embryos.

They report in the Oct. 1 issue of Developmental Biology that constant darkness delayed differentiation of these neurons, causing an accumulation of immature cells and a reduction in neuronal processes (axons and dendrites). Addition of melatonin to embryos kept in constant darkness reversed these effects, while blocking melatonin in embryos kept on a normal light-dark cycle mimicked the effects of constant darkness.

The results suggest that light and melatonin regulate these aspects of brain development, which may provide new insights into the genesis of disorders like autism, which has been associated with alterations in melatonin.

The research was supported by grants from the National Institute of Child Health and Human Development and the National Institute of General Medical Sciences.

Melissa Marino


Averting a future oncologist shortage

To identify factors that influence whether hematology-oncology fellows choose academic careers or private practice, Leora Horn, M.D., and colleagues surveyed hematology-oncology fellows at academic institutions.

In the Oct. 10 issue of the Journal of Clinical Oncology, the researchers report that less than half of the surveyed fellows believe a career in academic medicine is important, and approximately 40 percent of fellows graduating from academic institutions entered nonacademic careers. Factors associated with choosing an academic career included mentorship, research opportunities and a nurturing, intellectual environment. The results suggest that increased focus on these factors during fellowship training may improve efforts to retain fellows in academic careers.

The research was supported by a grant from the National Center for Research Resources.

Melissa Marino


Balancing act in the gut

The intestinal epithelial cells that line the gut form a barrier between the contents of the intestines – food, “good” microbes and harmful pathogens – and the rest of the body. Immune responses in this barrier must be balanced to protect against pathogens but not cause inflammatory diseases.

The immune response factor thymus leukemia antigen (TL) is selectively expressed in intestinal epithelial cells and interacts with T lymphocytes (white blood cells). Danyvid Olivares-Villagómez, Ph.D., Luc Van Kaer, Ph.D., and colleagues now report that TL expression promotes the development of inflammatory bowel disease and also protects against infection by the intestinal pathogen Citrobacter rodentium in mouse models. They demonstrate that TL expression pushes T cells toward a “Th17” response that contributes to inflammation and protection against pathogens.

The findings, reported in the Oct. 15 Journal of Immunology, identify TL as a critical factor for balancing the immune response in the gut, which could be important for the development of mucosal vaccines and therapies for inflammatory diseases of the gastrointestinal tract.

This research was supported with funding from the National Institute of Allergy and Infectious Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases.

Leigh MacMillan


We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012