Philippa Melamed
Ph.D.: Tel Aviv University 1998
M.Sc.: Biology, Tel Aviv University 1993
B.Sc.: Animal Sciences, Hebrew University, Rehovot 1991
Main Nano Field:
Researching protein-DNA interactions in regulating gene expression of hormones. This involves molecular biology techniques, microscopy and I'm planning to start also with some biophysical approaches
Research Interests
Connections between chromatin structure and gene expression
Hormonal induction of chromatin remodelling and gene transcription
Mechanisms of hormonally-induced gene splicing
Differentiation and development of the pituitary gland
Our research is aimed at understanding how hormones affect gene expression and cell function at the molecular level, and specifically the role and mechanism of targeting the chromatin. We are interested in the mechanisms through which the regulatory hormones induce chromatin and epigenetic changes to affect various aspects of physiology, especially in the endocrine and immune systems. Our main model is the gonadotrope of the pituitary gland which controls reproduction through the production of the gonadotropic hormones, LH and FSH.
Gonadotrope activity and the synthesis of these hormones are regulated primarily by the hypothalamic gonadotropin releasing hormone (GnRH), with additional feed-back regulation from gonadal hormones. Following a long period of quiescence since soon after birth, puberty signals a reawakening of gonadotrope activity and production of LH and FSH in response to elevated levels of GnRH. The gonadotrope thus provides an interesting dynamic and hormone-inducible model for the regulation of gene expression which is mediated through changes at the level of the chromatin, transcription, splicing and post-translational modifications.
We are currently focusing on understanding how GnRH-activated pathways induce changes in the chromatin at these gene loci. We have found that GnRH induces a number of histone modifications, and are studying the precise mechanisms of their induction and the consequence of the modification in downstream events. We are using high-throughput proteomic and genomic methods to identify and understand the nature of the GnRH effect on these cells through targeting diverse genes and proteins, and are also developing biophysical approaches to examine the protein-protein and protein-DNA interactions at the single-molecule level. In addition, we employ computational approaches to elucidate the various aspects of GnRH signaling towards the gonadotropin genes.