Melissa M. Harrison
6204B HF DeLuca Biochemical Sciences Building
440 Henry Mall
Madison WI 53706-1535
A.B., Harvard University
Ph.D., M.I.T. (H.R. Horvitz)
Postdoctoral, University of California, Berkeley (M.R. Botchan & T.W. Cline)
Transcriptional regulation during development
Following fertilization, the single cell of the zygote must divide and differentiate into all of the diverse tissue types of the adult organism. Because every cell has the identical DNA genome, this process is driven by coordinated changes in gene expression. We are broadly interested in how information encoded in this genome is interpreted during organismal development. We study conserved developmental processes to understand how changes in gene expression drive cell identity. Because these events are conserved, we leverage the wide variety of tools available for studies in Drosophila melanogaster, including biochemistry, genetics, molecular biology, genomics, and cell biology.
Activation of the zygotic genome
The initial stages of embryonic development are controlled by maternally contributed mRNAs and proteins. Immediately after fertilization, the genome is reprogrammed, allowing for the transition from a specified germ cell to the pluripotent cells of the early embryo. The zygotic genome remains transcriptionally silent during this reprogramming. Only at later cell cycles is widespread zygotic transcription initiated. This zygotic genome activation is tightly coordinated with the degradation of maternally provided mRNAs at the maternal-to-zygotic transition (MZT). Thus, during this discrete developmental time point the transcriptional profile of the developing embryo undergoes a monumental reorganization. We are focused on determining the mechanisms that reprogram the zygotic genome and drive transcriptional activation.
Epithelial cell-fate specification
Grainy head is a transcription factor conserved from fungi to humans with a shared role in driving epithelial cell fate. In humans, Grainy head has been implicated as both an oncogene and a tumor suppressor. To better understand how a single transcription factor can promote tumorigenesis in some cell types and prevent it in others, we have used mechanistic studies to determine the role of Grainy head in normal development. We have shown that Grainy head is bound to the same regions of the genome in the early embryo and three days later in the larva. Nonetheless, the genes that depend on Grainy head for proper expression depend on developmental stage. Thus, development regulates the activity, but not the binding of this essential transcription factor. Ongoing research seeks to understand how Grainy head activity is regulated and will provide insights into how this single transcription factor can both promote and repress metastasis.
Modeling human disease
We use the Cas9-genome editing system we developed in collaboration with the labs of Kate O’Connor-Giles and Jill Wildonger to model human disease in Drosophila. Using the vast array of tools available for studies in Drosophila, we are able to provide mechanistic insights into human disease.
Areas of Expertise
- Biomolecular Folding & Interactions
- Developmental Biology
- Gene Expression & RNA Biology
- Quantitative Biology