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ALLISON L. ABBOTT
Assistant Professor
B.S., 1995, College of William and Mary, Williamsburg, VA
Ph.D., 2000, Tufts University, Boston, MA
Post-doctoral Fellow 2000-2001, Tufts University, Boston, MA
Post-doctoral Fellow 2001-2006, Dartmouth Medical School, Hanover, NH
WLS 308
(414) 288-4422
email: allison.abbott@marquette.edu
Functional analysis of microRNA genes during C. elegans development
The overall focus of research in the Abbott lab is on the functional analysis of microRNA genes in C. elegans, identification of downstream microRNA targets, and specifically on the mechanism whereby members of the let-7 and lin-4 families of microRNAs cooperate to specify developmental timing decisions during larval development.
The ability to appropriately regulate gene expression is central to the normal development and function of cells, tissues and organisms. Small, non-coding, ~22 nucleotide RNAs, termed microRNAs, are now recognized as critical regulators of diverse cellular processes including cell proliferation, differentiation, and apoptosis and are almost certainly involved in human diseases. However, because there is a paucity of genetic data on the functions of specific microRNAs in vivo, both the normal regulatory and developmental pathways controlled by microRNAs, as well as pathways misregulated in cancers or other human disease conditions, are largely unknown. As an eminently genetically tractable animal, C. elegans provides an ideal model system in which to study the functions of microRNAs in eukaryotes, particularly as many microRNAs show complete or near-complete conservation between worms and humans.
MicroRNAs were first identified as regulators of developmental timing in C. elegans. Regulation of embryonic and post-embryonic development (larval stages L1-L4) requires the coordinated specification of cell fates in time and space. Mutations in “heterochronic” genes cause certain cells to adopt fates normally associated with earlier or later times in development, relative to stable temporal landmarks such as progression through the molting cycle. The lin-4 and let-7 microRNAs are critical regulators of temporal patterning decisions during early and late larval development, respectively. The let-7 family members, mir-48, mir-84 and mir-241, function cooperatively to regulate developmental timing decisions and regulate the temporal transition from the second to the third larval stage (L2-to-L3) through the regulation of a downstream effector, hunchback-like 1 (hbl-1).
Specifically, work in my lab is focused on the following areas:
- Which microRNA genes function to regulate larval development in C. elegans? What are the downstream target mRNAs controlled by these microRNAs?
- How do the lin-4 and let-7 families of microRNAs control developmental timing?
- How do the heterochronic genes, including hunchback-like 1 (hbl-1), control the L2-to-L3 developmental transition? What genes function downstream of hbl-1 to control cell fate decisions in the hypodermis of the worm?
Work in my lab will provide an opportunity to use molecular and genetic techniques to address fundamental questions of how microRNAs function to control animal development.
Selected References:
*Abbott A.L., *Alvarez-Saavedra E., *Miska E.A., Lau N.C., Bartel D.P., Horvitz H.R., Ambros V. (2005). The let-7 MicroRNA Family Members mir-48, mir-84, and mir-241 Function Together to Regulate Developmental Timing in Caenorhabditis elegans. Developmental Cell. 9:403-14
Abbott, A.L. (2003). Heterochronic genes. Current Biology. 13: R824-25.
