I received my PhD from the University of Cape Town. My PhD training involved the reconstitution of purified histones onto defined DNA templates to investigate the effect of negative supercoiling of the DNA on the formation and positioning of nucleosome cores in vitro. I then proceeded with post-doctoral training at the NIH and at Pennsylvania State University. During my post-doc I studied chromatin in situ in Saccharomyces cerevisiae in the laboratory of Robert T. Simpson. I investigated the effect of a nucleosome positioned over the TATA box of a mating type-specific gene promoter on the expression of the gene, and showed that by systematically shifting the position of the nucleosome on the promoter, the level of expression of the downstream gene could be modulated. I also investigated the role of DNA curvature in nucleosome positions, as well as the molecular mechanism involved in the formation of silent chromatin domains. I finally identified and characterized the yeast linker histone H1 in my post-doc.
I returned to South Africa in January 1998 and was appointed as Senior Lecturer at the University of the Free State, where I set up my lab and continued my work on the role of chromatin in gene regulation. I was awarded a Wellcome Trust International Senior Research Fellowship in 2000, and continued to study the role of linker histones in the regulation of gene expression at the University of Cape Town. My laboratory performed genome-wide ChIP-chip analyses, and showed that the linker histone preferentially associated with the yeast genome in stationary phase. The level of binding was related to transcriptional levels at different positions in the genome. To investigate the possible role of the H1 in domain wide gene regulation, I developed a statistical approach, implemented in software that I developed, that analyzed the statistical significance of physical clusters of genes in transcriptomic data. Making use of public datasets, I showed that silencing proteins such as Sir1 and Rap1 was involved in domain wide gene silencing. There was also evidence that H1 was involved in the chromatin-mediated repression of gene domains.
I have been actively involved in chromatin research, studying the role of chromatin in gene regulation. I have adapted and actively contributed to high throughput analyses that transformed chromatin and gene regulation studies into the field that became known as epigenetics, and, with the advent of genomic techniques, as epigenomics.