Research in my laboratory focuses on the molecular genetics of two model organisms: Canis familiaris
(dogs) and Saccharomyces cerevisiae (yeast). One of the revolutions of the last decade has been our ability to determine the complete DNA sequence for a number of organisms, including humans. Although many aspects of the genetic code are known, we still don't know exactly how the sequence of bases in DNA specifies how much of a particular gene product is to be made, or in what types of cells or under what conditions.
We also do not know the real function of many of the gene products identified by computational methods in sequenced genomes. My research is done as a collaboration with undergraduate students and is currently focused on two questions:
- What genes affect body size and behavioral differences in different breeds of dogs?
- How do signals at the end of genes regulate their expression levels and regulation?
Purebred dogs are an excellent model system in which to understand how genes affect particular behaviors and characteristics of body shape and size. Selective breeding by humans has led to the creation of hundreds of different breeds of dog that vary in appearance and in behavior.
We have focused on two types of genes in dogs: those that affect behaviors in working and non-working retrievers and those that affect body size. Retrievers have been selected for more than a hundred years for the ability to retrieve game.
More interestingly, breeders in several breeds of retrievers (Labrador and Golden Retrievers in particular) have differed in what traits were selected in planning breedings.
The result of this has been to create different breeding pools of “working” and “non-working” types in the breed. We are using quantitative measures for behaviors to identify genetic differences between working and non-working dogs within these retriever breeds.
We are also looking at variation in particular candidate genes (DAT1, DRD4) for effects on retrieving behaviors.
In collaboration with the Ostrander laboratory (at the National Institutes of Health) and the Sutter laboratory (at the College of Veterinary Medicine at Cornell) we also investigate genes that affect body size in dogs.
Our current research focuses on variations in genes that appear to be particularly important in dogs of very large and very tiny breeds.
I have had a long-standing interest in the arrangement of regulatory signals at the beginning and end of genes and how they affect the regulation of gene expression. I became interested in the signals at the end of genes (polyadenylation sites) when we discovered that the gene SUA7, which encodes an essential transcription factor, showed a phenomenon called “alternative polyadenylation”.
In alternative polyadenylation, the mRNAs made from a gene end at two or more sites. In the case of SUA7, which one of two sites is used depends on the conditions under which the yeast are being grown. We are trying to understand signals that contribute to alternative polyadenylation and how the cell chooses between alternative sites using a whole genome approach.
We are using bioinformatics tools to predict where polyadenylation takes place in yeast genes and compare the predictions to the site at which we find polyadenylation takes place experimentally. We are also testing genes which show alternative polyadenylation for changes in site choice under different growth conditions and identifying the important DNA sequence elements for regulated site choice.