Daniël P. Melters, Ph.D.
How are chromatin domains formed and how are they maintained? How can a chromatin domains exist in both a diffuse state and as a descrete locus while maintaining it's well-defined function? How do histone variants, in combination with nucleosome-binding proteins, orchestrate the functional aspects of the chromatin fiber? The centromere, defined by centromere-specific proteins such as the histone variant CENP-A, is an ideal model system, as its genomic organization is dramatically different between species. Budding yeast has point centromeres, humans have regional centromeres, whereas nematodes are holocentric. Nevertheless, the role of centromeric chromatin remains the same. Using biochemical and biphysical tools, Dr. Melters, dissects how chromatin accessibility is modulated by histone variants and chromatin-binding factors.
1) chromatin biology, 2) centromere, 3) genome evolution, 4) atomic force microscopy (AFM), 5) high-speed AFM
Intrinsic elasticity of nucleosomes is encoded by histone variants and calibrated by their binding partners.Proc Natl Acad Sci U S A .. 116(46): 24066-24074, 2019. [ Journal Article ]
- Genes (Basel). 6(3): 751-76, 2015. [ Journal Article ]
Comparative analysis of tandem repeats from hundreds of species reveals unique insights into centromere evolution.Genome Biol. 14: R10, 2013. [ Journal Article ]
- Chromosome Res. 20: 579-93, 2012. [ Journal Article ]
- Proc Natl Acad Sci USA. 106: 7804-9, 2009. [ Journal Article ]
Daniël originally comes from the Netherlands. He received his Bachelor's and Master’s degree in Biomedical Sciences from the Leiden University, the Netherlands. For his M.S .degree, he worked in Dr. Lipsky’s lab at the NIH/NIAMS, studying the B lymphocyte immunoglobulin heavy chain repertoire. For his MS thesis Daniël joined Dr. De Kloet’s lab at the LACDR/Leiden University, where he identified single nucleotide polymorphisms (SNPs) in the mineralocorticoid receptor gene of different inbred mouse strains. Following his M.S., he moved to San Francisco where Daniël joined Dr. Pearce’s lab at UCSF. Here he worked on elucidating the aldosterone-signaling pathway that regulates sodium reabsorption in kidney epithelial cells. For his Ph.D., Daniël joined the labs of Drs. Ian Korf and Simon Chan at UC Davis. In this collaboration, he used bioinformatic tools to identify candidate centromeric tandem repeats across the eukaryotic tree. In addition, he joined the biotechnology program, which led to an internship at Genentech. In 2014, Daniël joined the LRGBE/CSEM as a Postdoctoral Fellow, where he works under the guidance of Dr. Yamini Dalal, studying the structural features of centromeric chromatin, what makes it unique and to determine its functional consequences. His interests outside the lab include, but are not limited to, racing cars, his family, reading about current affairs and history, and science policy.