In my lab we study chromatin architecture by looking at nucleosome positioning and its relation to the underlying DNA sequence in the genome, with the goal of learning how to modulate chromatin architecture by subtly manipulating the underlying DNA sequence to regulate gene expression. We are using both in vivo (in live animals) and in vitro (in the test tube) approaches in our studies coupled with ultra-high-throughput DNA sequencing technologies. For these studies we use the nematode worm C. elegans (a common model organism for human genetics and disease). We are also using in vitro nucleosome reconstitution assays to define and test putative nucleosome attractive or repulsive sequences. These sequences can then be tested in vivo in the worm for their potential to regulate genic expression both temporally and spatially in C. elegans.
Because of the highly conserved nature of histone proteins within the domain Eukaryotae and the absolute conservation of the chemical structure of DNA between all forms of life, what we learn from these basic studies in the worm may enable us to subtly manipulate gene expression in human cells and tissues with the potential to overcome the universal problem of gene silencing which occurs with DNA-based disease treatments such as those seen in current applications of gene-therapy.
