Barry M. Honda

Areas of interest

Our work has had two long term objectives:

(i) to contribute to the physical mapping/ sequencing/ functional annotation of Drosophila centric heterochromatin, as a model for metazoan genomes, and
(ii) in parallel, to study the structure, function and evolution of genes in centric heterochromatin.

Heterochromatin is defined as the darkly-staining, densely-compacted part of chromosomes, generally found near centromeres and telomeres. One defining characteristic of heterochromatin is its high levels of repeated DNA sequences, which make genome sequencing and molecular analysis very challenging. In Drosophila, a large proportion of the genome (up to 1/3) is found packaged in heterochromatin, and it has been extremely difficult to study genes in these regions, because most standard fly genetic and molecular tools are not available.

We have been working on a genetic map to identify essential genes in the centric heterochromatin of Drosophila chromosome 3. The task requires special genetic methods--generating and characterizing large deletions (Deficiencies/Dfs) of DNA within heterochromatin—followed by use of these Dfs to isolate mutations, which allow us to study previously uncharacterized genes. The work serves to link the genetic and physical maps of chromosome 3 heterochromatin, as well as generating powerful genetic and molecular tools to study genes in these poorly understood regions of the genome. This work has been complemented by studying the same genes in other Drosophila species, to identify important features conserved during evolution.

Our results to date have made contributions to genomics and the functional annotation of heterochromatic DNA sequences. The work has also provided new insights into the expression and regulation of a number of interesting heterochromatic genes, many of which are involved in critically important cellular processes.