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Stephen Caster

Stephen Caster

Graduated with a Ph.D. in Genetics, August 2016

Advisor: Dr. Deb Bell-Pederson

Room 210 Biological Sciences Building West
Department of Biology
MS 3258

College Station , TX 77843-3258
Office Phone: (979) 847-9239

Education:

  1. B.S. in Agronomy, Texas A&M University
  2. M.S. in Soil Science, Texas A&M University

Biography:

Entered the program in 2008.  Worked as a teaching assistant for the Soil Microbiology Lab for two years and for the Genetics Lab for a year and a half.   Current work includes looking at the outputs from the mitogen-activated protein kinase (MAPK) pathway in Neurospora crassa, specifically with regards to transcriptional and translational regulation.

Research Project:

I am interested in how the circadian clock regulates translation in Neurospora crassa. Circadian clocks provide an endogenous mechanism to regulate biological functions ranging from sleep-wake cycles to metabolism and gene expression, however post-transcriptional regulation of clock outputs is not well understood. The circadian clock in Neurospora crassa signals through rhythmic activation of conserved mitogen-activated protein kinase (MAPK) pathways, including the well-characterized p38 osmosensing (OS) MAPK pathway. The clock regulates rhythms in the phosphorylation of the MAPK OS-2 (P-OS-2), such that OS-2 is phosphorylated and active during the day. P-OS-2 then phosphorylates downstream targets, including transcription factors, chromatin modification proteins, and kinases, which lead to rhythmic control of pathway outputs. I have shown that clock control of P-OS-2 leads to rhythmic phosphorylation and activation of a conserved serine/threonine kinase, RCK-2. Clock-controlled RCK-2 rhythmically phosphorylates and inactivates the highly conserved eukaryotic elongation factor 2 (eEF-2), with the peak in eEF-2 phosphorylation occurring at mid-day. However, it is not known if rhythmic inactivation of eEF-2 leads to rhythmic translation of most mRNAs through global repression of translation elongation, or if specific mRNAs are targeted for translational repression. Results from experiments to determine if clock regulation of eEF-2 affects overall levels of translation, and rhythmic ribosomal profiling in wild type (WT) and RCK-2 mutant cells, are currently being analyzed. In addition, comparison of rhythmic ribosome profiling data in WT versus clock, or RCK-2, mutant cells with the transcriptome data from the same cells, will reveal the extent of clock control of translation, and the impact of rhythms in the activity of eEF-2 on this process.

Broader Impacts of Research Project:

I am interested in how the circadian clock regulates translation in Neurospora crassa. Circadian clocks provide an endogenous mechanism to regulate biological functions ranging from sleep-wake cycles to metabolism and gene expression, however post-transcriptional regulation of clock outputs is not well understood. Using ribosome profiling (to look at all actively translating ribosomes) and transcriptome data (to look at total mRNA levels), I will determine what mRNAs are being translated throughout the day.  I will also identify if there is any differential regulation between mRNA and protein levels.  To determine the role of the clock in translation regulation, I will compare samples from a wild-type (WT) strain to samples from two mutant strains (a clock deficient strain and a strain with constitutive signaling from the clock).  Because of the highly conserved nature of the ribosomal machinery, what we find in Neurospora will lead to a better understanding of the mechanism for clock regulation of translation in higher Eukaryotes.