Past
- After graduating from high school in Ogden, Utah, I attended the University of Utah in Salt Lake City. I received a Bachelor's of Science in Biology in 2004. While studying, I worked for a short time in the lab of Dr. Darryl Kropf. The research focused on the determination of cell polarity during early development in the alga S.compressa.
Pending
- I am currently working in the lab of Dr. Marla Berry at the John A. Burns School of Medicine, University of Hawaii at Manoa. The lab focuses on the characterization of human selenoprotein families and the selenoprotein translation machinery. I will begin the PhD program in the Cell and Molecular Biology department at the University of Hawaii in the Fall ('05).
Research Interests
- Selenocysteine: the role of the 21st amino acid in the evolution of
protein function.
Selenium is an essential micronutrient among organisms as diverse as bacterias and mammals (including humans). It is mainly found within selenoproteins in the form of selenocysteine (Sec), the 21st amino acid. In brief, Sec is inserted by dynamic recoding of a UGA stop codon in protein translation due to several cis and trans-acting factors (REF). In eukaryotes, the main cis-factor is an mRNA hairpin structure, the SElenoCysteine Insertion Sequence (SECIS), located in the 3'UTR of selenoprotein genes.
It has been established that dietary selenium, besides regulating the redox state of the cell, plays an important role in cancer prevention (Combs et al., 2001), immune function (Ursini et al., 1999), aging (Martin-Romero et al., 2001), male reproduction (Ursini et al., 1999), and other physiological and pathophysiological processes (Rayman, 2000). Selenium deficiency is known to affect thyroid function and it is linked to Keshan Disease where enlarged heart and poor heart function is observed (Levander and Beck, 1997). On the other hand, high blood levels of selenium can result in a condition called selenosis (Koller and Exon, 1986). Symptoms include gastrointestinal upsets, hair loss, white blotchy nails, and mild nerve damage. Selenoproteins are thought to be responsible for most biomedical effects of dietary selenium and are essential to humans, but the lack of insight into the molecular role of Sec and Sec-containing proteins compromises our comprehension of the selenium role.
Interestingly, cysteine (Cys) is frequently found in place of Sec in homologous proteins across the eukaryotic lineage, hence, these two residues are exchangeable in protein function and Sec, per se, does not possess an essential role. In agreement, mutational change of the Sec residue to Cys also gives variants that are active (Axley et al., 1991, Berry et al., :1992} but have a lower overall catalytic efficiency (Axley et al., 1991), possibly due to the lower pKa in Se (REF). Furthermore, Cys-containing proteins can be as active as Sec-proteins if additional residues are mutated accordingly Gromer et al., 2003). Therefore, the predilection for Sec or Cys among proteins and lineages is puzzling.
However, such uneven use of Sec and Cys permits one to gain comparative insight into the properties and functions of Sec and, thus, of selenoproteins.
- Research Objectives:
I plan to identify homologs of interest to known selenoprotein families, either in Sec or Cys form across the three domains of life. In addition to simply 'BLASTing' for homologs, profiles of known selenoproteins will be constructed in order to insure that our searches are both highly sensitive and highly specific. These profiles will also be used for the quick and easy identification of selenoproteins within more genomes as they become available.
I plan to study the pattern of Sec/Cys exchange between orthologous proteins, specifically the loss or gain of Sec usage among taxa. The construction of a phylogeny indicating ancestral states and times since divergence will be very useful.
I plan to compare such pattern to Se availability, Sec incorporation efficiency, selenoprotein activity and others. This will lead to a classification of selenoproteins according to their phylogenetic dependence on Se.
I plan to specifically study the selenoprotein SelP. This is the only eukaryotic protein with more than one Sec residue (ranging from 10 to 17 residues in different species). I want to investigate which Sec residues are critical and conserved as such across the eukaryotic lineage.
I plan to study the causes and effects of the Sec/Cys exchange from both an evolutionary standpoint and a functional cellular view.
Publications
- Any day now...
Presentations
- Lab Meetings:
- R. Stillwell
SelenoDB: a comprehensive database for information on eukaryotic and prokaryotic selenoproteins and related genes and proteins.
Download - R. Stillwell
Understanding the trends of Sec/Cys usage.
Download - Posters:
- R. Stillwell, M. Berry, S. Castellano
How ancient are selenoproteins?
Download