Angie Hilliker's Lab
A cell constantly alters the expression of its genes (and thus the proteins it makes) in order to respond to its environment or change its function. Gene expression can be modulated at many levels, from the birth of a messenger RNA (mRNA) to its destruction. Once it enters the cytoplasm, an mRNA can have various fates– it can be translated, translationally repressed, localized, or degraded. The function of the mRNA is determined by the proteins that associate with it to form an mRNP (mRNA-protein complex). For example, a translating mRNA associates with the ribosome, which will use the mRNA to make a protein. Alternatively, a non-translating mRNA associates with translational repressors or decay factors that sequester the mRNA from the ribosome or destroy the mRNA. The mRNP composition is dynamic, which allows the mRNA to move among translation, translation repression, or decay complexes. We study how mRNPs alter their composition to change the translatability of the mRNA. We use budding yeast and a combination of genetics, cell biology, and biochemistry to understand how a cell determines the fate of an mRNA. This type of regulation of translation is important in all cells, but is especially important early in development, during stress, and in learning and memory.
Current Projects
Our current projects revolve around the DEAD-box ATPase, Ded1, and its role in promoting the translation of repressed mRNAs. These projects include:
- Using genetic screens to identify factors that help or inhibit Ded1 function in vivo.
- Studies of the post-translational modifications of Ded1 and their affect on Ded1’s ability to bind RNA, bind and hydrolyze ATP, and affect translation.
- In vitro translation assays to understand the mechanism of Ded1’s role in promoting translation.
- Microscopy analysis of cytoplasmic RNA granules as tools to track pools of non-translating mRNAs.
- Genetic screens to identify in vivo targets of Ded1.
- Genetic screens to identify other factors involved in regulating cytoplasmic mRNA.
Current Lab Members
Erica Trujillo '14
Audrey Kindsfather '15
Kenton Meronard '15
Nick Rothbard '15
Gillian Hess '16
Jacob Shapiro '16
Hema Pingali '17
Aidan Winters '17
Maria Zaporozhets '17
Lab Alums
John Gallon (exchange student from Queen Mary, University of London, 2012)
Chris Hooper (UR '12)
Marisa Jendras (UR '12)
Beth Pollard (UR '13)
Lisa Fronek (UR '13)
Sean Robbins (UR '15)
Helen Warner (UR '15)