Affiliation(s):

• Professor and Chair, Department of Biological Sciences, Wayne State University

I studied Art and Design for a year but left college and worked for several years. Then I started back at a community college and ultimately received a BS in Biochemistry from Cornell University. My PhD, for studies of insect endocrinology, was from the University of North Carolina at Chapel Hill.

Humans and fruit flies both have XX females and XY males. This produces an imbalance in gene dosage that is lethal if not corrected. Male flies deal with this challenge by increasing expression from genes on their single X to match the output of the two female X chromosomes. The process of correcting for X-linked gene dosage in mammals is very different, but both species rely on chromatin modifiers that are selectively recruited to a single chromosome. The composition and regulatory activity of these modifiers is quite well-studied. In contrast, how a single chromosome is identified with the required selectivity remains mysterious. We use genetic and molecular approaches to explore this remarkable phenomenon in fruit flies.

Completely by accident! I was working on a fly gene that was possibly involved in learning and memory. The gene, now named roX1 (RNA on the X chromosome 1), was expressed only in males and does not encode a protein. When I performed in situ hybridization to determine where roX1 was expressed I was amazed to discover the RNA localizing along the length of the X chromosome in all male cells. Just a few years earlier researchers had discovered a long, non-coding RNA called Xist (X inactive specific transcript) that localizes to one X chromosome in mammalian females and has a central role in identifying this chromosome. It turned out that roX1 is one of two long non-coding RNAs that are necessary for recognition of the male X chromosome in flies. My laboratory now uses mutations in the roX genes to explore the mechanism of X recognition.

The intersection of gene expression, nuclear architecture and organization is a particularly fertile area right now. Nuclear organization is implicated in X chromosome recognition in both mammals and flies. My students are investigating candidate genes that participate in nuclear organization and have identified a few that participate in X recognition. Our goal is to arrive at a more complete picture of how nuclear structure contributes to selective recognition of a single chromosome.

This would have to be the papers, now almost 40 years old, in which Tom Cline deduced a key aspect of sex determination in flies by examining Sexlethal (Sxl) alleles. Sxl induces female development and is turned on in embryos with two X chromosomes. Sxl blocks increased expression of the X, which only occurs in males. Finally, Sxl positively autoregulates itself. Cline characterized a series of Sxl mutations and, years before the sequence of this gene was known, described these functions with remarkable detail and accuracy. These studies are a model for the power of logic and genetic analysis.

My mother was very knowledgeable and curious about the natural world, especially birds and plants. Although I did not recognize it at the time, this gave me foundational knowledge that I have built on ever since.

I love to spend time outdoors hiking and birdwatching.  Some gardening and a lot of reading.