Omid Toub
OMID TOUB. MSc DEFENSE PROGRAMME
B.Sc., University of British Columbia, 2002
Exam location:
Life Sciences Center, Rm 1516, 2350 Health Sciences Mall, UBC
EXAMINING COMMITTEE
Chair: Dr. Carolyn J. Brown (Department of Medical
Genetics)
Supervisory Committee:
Dr. Thomas A. Grigliatti (Department of Zoology)
Dr. Hugh W. Brock (Department of Zoology)
University Examiner:
Dr. Cornelius Boerkoel (Department of Medical Genetics)
ABSTRACT
Emergence of the higher eukaryotic organisms from their
prokaryotic ancestors has been closely associated with an increase of the
genetic material. This progression has been dependant on machineries that can
package the DNA to various extents, from the levels seen in the 30 nm fibers of
interphase nuclei to that of metaphase chromosomes. These evolutionary changes in genome organization have
correlated with advancements in regulation of gene expression during
development. In eukaryotes, cellular differentiation is partly dependent on the
mechanisms that would silence the correct genes in a particular tissue and
maintain this silenced state throughout subsequent stages of development. To understand the factors involved in such
mechanisms many labs, including ours, have used position effect variegation
(PEV) to identify proteins that form or remodel the chromatin fiber. Genetic
screens have identified S2214, and puckered as genes coding for putative
modifiers of PEV. The aim of this thesis, is to characterize S2214, and
puckered by addressing two main questions: i) do the mutations in each of these
genes modify the phenotype observed in PEV? And ii) do their products localize to the nucleus, and if so
to the chromatin? Results show that P element mutations in these genes cause
dominant and strong suppression of PEV in wm4 and SbV. Moreover, the observed Su(var) activity
is reverted upon mobilization of the P elements. I developed and purified an
antibody for each gene. Puc, the
product of puckered, localized to the nucleus of S2 and KC1cells (which are
late embryonic Drosophila cell lines), as well as the nuclei of salivary gland
cells of Drosophila melanogaster, but could not be detected on the polytene
chromosomes. In addition, S2214, the product of S2214, was found in the nuclear
fraction of S2 cells, and could be observed within the nuclei of S2 and KC1
cells as well as those of the salivary glands of Drosophila melanogaster. Furthermore, S2214 was found at several
interbands of the polytene chromosomes of these salivary glands. It is our
conclusion that gene products of both S2214 and puckered are involved in
mechanisms that affect chromatin structure.
AWARDS
Winner of a Graduate TA Teaching Award (2005/2006)
PRESENTATIONS
Medical Genetics research day poster presentation (Nov
2005): Initial characterization of
S2214 and puckered as suppressors of position effect variegation in Drosophila
melanogaster.
Medical Genetics research day poster presentation (Nov
2006): Puckered’s role in position effect variegation may be separate from its
role in the JNK pathway.
Canadian Society of biochemistry and molecular and
cellular biology “Epigenetics and Chromatin Dynamics” conference at Banff
(march 2008): S2214 is a strong suppressor of Position Effect Variegation and
directly interacts with chromatin. Omid Toub1 and Thomas A. Grigliatti2
COURSES
Zool 500A: Directed studies in Zoology, Dr. Grigliatti
MEDG 520: Advances in Human Molecular Genetics, Dr.
Lorincz
MEDG 530: Human Genetics,
Dr. Friedman
MEDG 545: Current Topics in Medical Genetics Research, Dr.
Brown
MEDG 548: Directed Studies-Protein Biochemistry,
Dr. Grigliatti
Gene 502: Genetics, Dr. Brock
Biol 548: Advanced topics in biologicalmicroscopy, Dr. Wasteneys