My students and I use a molecular genetic approach to answer interesting biological questions about the genetic basis of behavior. That is, we look at the effect of the expression of certain genes on the behavior of an animal, including the animal’s ability to sense and respond appropriately to its environment. The animal we study is a small free-living roundworm, Caenorhabditis elegans. This small (1 mm) worm can be found eating bacteria in your compost pile. Despite its small size and seeming simplicity, this worm is capable of sensing chemicals in the air (smell) and in liquid (taste), it has a sense of touch (mechanosensation), and it can learn and remember things. Male C. elegans also have a complex mating behavior. We are interested in how these behaviors are manifested; specifically, we want to know which genes need to be used and which proteins need to interact in order to allow these behaviors to take place.
We have completed a study of the role of a putative potassium channel in male mating behavior. Students in my lab isolated interesting alleles of the gene sup-9, thought to encode a potassium channel. These mutant alleles visibly affect male worms, making them unable to mate because they do not move as elegantly as they should. This work sas funded by several grants from the NIH-AREA program.
In 2009, I spent six months working at the Karolinska Institute in Sweden, collaborating with Dr. Peter Swoboda. We are continuing to collaborate on a project to determine which genes are needed to maintain neuronal synapse function in adult worms. The Swobada lab already demonstrated that reductions in a particular neuronal protein, DAF-19, that encodes a transcription factor, reduces neuron-neuron communications (synaptic transmission) similar to what is seen in early hallmarks of diseases such as Alzheimer’s. We are using C. elegans as a model system to determine which genes are controlled by the DAF-19 transcription factor and that are needed to maintain synaptic functions. A genome-wide screen of the transcriptome of mutant and wild type worm populations has provided us with a list of 174 possible genes to study! Students who currently work in my lab learn techniques such as PCR, site-directed mutagenesis, molecular cloning, production of transgenic worms, bioinformatics, confocal microscopy, and basic genetics.
In a related project, we are working to determine whether the genes identified as perhaps being controlled by the DAF-19 transcription factor share a similar enhancer or promoter sequence (to which DAF-19 or its partners might bind). Chelsey Sand, pictured above, used a bioinformatics approach to compare the sequences upstream of the genes we are studying to find common sequences. We call the sequence she identified the SandBox!
