Randerson Foundation MRes/PhD Studentship: Role of Rho Kinase in the Developing and Mature Heart Muscle

Faculty of Medical Sciences

Newcastle University

Reference Code: HG039

Closing Date: 29th February 2012

Supervisors: - Dr H Phillips and Professor D Henderson ( Institute of Genetic Medicine )

In response to stress on the adult heart, developmental pathways can be reactivated, suggesting that factors that play crucial roles in normal development may be involved in disease processes in adult life. We hypothesize that Rho Kinase (ROCK) may be such a protein. ROCK is required in the early heart and has been shown to be involved in the transition from hypertrophy to heart failure in diseased mouse and human hearts.

For several years, we have used ROCK dominant-negative (DN) mice to downregulate the function of ROCK. The DN protein can be expressed in a cell specific manner, blocking downstream signalling from the two isoforms of ROCK (ROCK1 and ROCK2) and thus overcoming functional redundancy. In preliminary studies, dominant negative ROCK expressed specifically in developing cardiomyocytes (using the Mlc2v-Cre transgenic mouse), resulted in abnormal arrangement of the cardiomyocytes.

We therefore hypothesize that ROCK plays an essential role in maturation of the heart muscle. This hypothesis will be tested by: 1) examining the effect of downregulating ROCK in the developing myocardium, 2) elaborating the signalling cascade downstream of ROCK, 3) determine if DNROCK disrupts the adult heart. The successful candidate will achieve this through studying transgenic mice which allow us to target the downregulation of ROCK specifically in the muscle cells. The student will gain experience in a range of techniques including histology, immunohistochemistry, analysing cardiac function, molecular biology, cell culture and mouse genetics.

Duration of the award - 4 years (an MRes Programme in the Faculty of Medical Sciences followed by a three year PhD)

Person Specification
The successful applicant should have a BSc in Biological Sciences with at least a 2 (i) and should be self-motivated, be able to work independently as well as part of a team, and have excellent communication and time management and organisational skills. An interest in cardiac development is advantageous.