Dr. Danielle Vermaak
Danielle was born in South Africa and grew up in Port Elizabeth and Pretoria. She received a Bachelors degree from the University of Pretoria in 1989, majoring in Biochemistry and Chemistry. Danielle moved to Cape Town University to persue her interest in protein-DNA interactions. For her masters thesis she purified a poly(dG)-binding protein from sea urchin embryos, and used DNA footprinting techniques to characterize its DNA binding properties. Danielle moved to the United States in 1993, working as a technician at the National Institutes of Health for one year, studying the genes that are turned on during metamorphosis in frogs. During her graduate research in Alan Wolffe's lab at the NIH, Danielle worked on transcriptional repression by histone H1 and histone deacetylase RPD3 in frog oocytes and embryos. Linker histones such as H1 help package nucleosomal DNA into higher order structures. In Xenopus, somatic histone H1 replaces the cleavage stage variant during gastrulation. This transition causes the repression of genes encoding the oocyte-type 5S rRNA and restricts the competence of ectodermal cells to differentiate into mesoderm. Danielle and colleagues showed that the globular domain of somatic H1 is sufficient for directing these changes, suggesting that compaction of nucleosomal arrays by charged H1 tail domains is not required. Another way in which genes can be turned off is through deacetylation of histone tails. Danielle cloned the RPD3 histone deacetylase from Xenopus and used oocyte microinjection experiments to show it functioned in transcriptional repression of reporter genes. This repression required deacetylase activity and nuclear import of RPD3 mediated by a carboxy-terminal nuclear localization signal. Danielle further characterized the interactions between RPD3, RbAp48 and histone H4. Histone deacetylase appeared to be directed to specific promoters through interaction with RbAp48 in the absence of sin3 co-repressor. Danielle received her PhD in Biology from Johns Hopkins University in 1999 and moved to Seattle to do a postdoc in Steve Henikoff's lab at the Fred Hutchinson Cancer Research center, working on evolutionary and molecular aspects of centromeric histone in (Cid) Drosophila. All centromeres require specialized chromatin containing a variant histone H3. Since the DNA sequence at centromeres is not conserved, the mechanism of localization of these variant histones is unclear. By making chimeras between Drosophila melanogaster Cid and Cid from a divergent species that was unable to target melanogaster centromeres, Danielle and colleagues showed that Loop I of the histone fold domain was a critical targeting determinant. Loop I is a known DNA-binding site of H3 within the nucleosome and is under positive selection in flies, as shown by Harmit Malik, also in the Henikoff lab at the time. This strongly suggested that DNA specificity is important for targeting, perhaps through discriminating loop I-DNA contacts during histone deposition. In the Henikoff lab, Danielle began studying Rhino, a heterochromatin protein 1 (HP1) predominantly expresed in the Drosophila ovary. Danielle is continuing this and other research projects as a staff scientist in the Malik lab. She is particularly interested in chromatin proteins evolving under positive selection. Elucidating the driving force of such selection can uncover novel biological functions of chromatin proteins and lead to a better understanding of the fixation of less than optimal alleles in populations. Heterochromatin commonly contains HP1 proteins defined by the presence of a N-terminal chromo domain and C-terminal shadow domain connected by a hinge region. Drosophila melanogaster flies have five HP1s. HP1a-like proteins bind to histone H3 methylated on lysine 9 and is required for the maintenance of heterochromatin. Rhino is different from the other HP1s because it is predominantly expressed during oogenesis and early development. This is an unusual expression profile for a protein presumed to have a structural function in chromatin. Upon examining the molecular evolution of Rhino in closely related Drosophila species, we found strong evidence for adaptive evolution, or selection for replacement amino acids changes. This selection for amino acid change is unexpected and striking in comparison to other HP1 proteins that are undergoing purifying evolution, i.e. selection against amino acid replacement changes. Current and future experiments are focused on identifying the driving force behind the positive selection of Rhino. Danielle is married to Chris Lausted, a research engineer at the Institute for Systems Biology. Danielle and Chris have two daughters, Maddie (almost 4 years) and Josie (1 year old). They live in Ballard, Seattle. More pictures of the family are available on her personal website (http://lausteds.com/danielle/).
Research Papers
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 Danielle Vermaak
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