Receptor Biology Research Unit

Co-Director:                   Prof A. A. Katz
                                E-mail: a.katz@uct.ac.za

                                           Dr. C.A. Flanagan
                                E-mail: colleen.flanagan@wits.ac.za

                                           Prof. R. P. Millar
                                E-mail: R. Millar@hrsu.mrc.ac.uk

The mission of the UCT/MRC Research Group for Receptor Biology is to study the structure and function of G protein-coupled receptors and to apply the research to understanding and treating diseases which have major effects on the social and economic welfare of South Africa. G protein-coupled receptors constitute the largest family of membrane proteins in the human genome and they are the targets of more than 50% of existing prescription drugs. These therapies are used to treat a wide range of disease, including reproductive, endocrine, cardiac and psychiatric disorders, pain and obesity. G protein coupled receptors also have important roles in cancer and infectious disease, especially HIV/AIDS. The Group focuses on three families of G protein-coupled receptors, namely:

• Gonadotropin-releasing hormone (GnRH) receptors. The GnRH receptor is the central regulator of reproductive function.  Analogs of GnRH are used clinically to treat infertility, sexual development disorders and cancers of the reproductive tract. In addition, GnRH directly inhibits growth of cells derived from reproductive tissue cancers. The Research Group for Receptor Biology has recently cloned the type II GnRH receptor, which has been shown to regulate mating behaviour in female primates. The Group studies structure-activity relationships of GnRH receptors in order to define how they bind GnRH, as a prelude to the development of orally active GnRH drugs. The Group is also studying the cellular signaling and regulation of the receptors and the molecular mechanisms underlying the anti-proliferative effects of the GnRH receptors in cancer cells.

• Prostaglandin receptors and their roles in cervical cancer. Cervical cancer is the most common cancer in women in developing countries, including South Africa. The Group studies the roles of prostaglandin receptors and their ligands in neoplastic transformation of the cervix. The Group is also studying the effects of prostaglandins that occur in high concentrations in seminal plasma on the development and progression of cervical cancer. 

• The CCR5 chemokine receptor and its role in HIV infection. The CCR5 chemokine receptor is the primary co-receptor used by the Human Immunodeficiency Virus (HIV) to enter and infect human cells.  Improved understanding of the interaction between CCR5 and HIV may lead to the improved design of vaccines and/or antiretroviral therapy.  The Research Group for Receptor biology is studying the functional consequences of CCR5 mutations that have been identified in southern African populations. The Group is also studying how the Envelope proteins of the major South African form of HIV (HIV-1 subtype C) interact with CCR5. The Group is also making progress in defining the underlying molecular mechanisms by which CCR5 enables HIV to fuse with and enter human cells, an essential early step in HIV infection.

• The Group plays an important role in capacity development and the training of postgraduate students at Masters and Doctoral levels as well as Post-doctoral Fellows in the field of G protein-coupled receptors which are a key target in drug discovery.

Service offered
Determination of GnRH levels in serum.