Dr Caroline Brennan
Lecturer
- Room: 6.26, Fogg building
- Telephone: +44 (0)20 7882 3011
- Email: c.h.brennan("at" sign)qmul.ac.uk
Research interests:
Research website: http://webspace.qmul.ac.uk/chbrennan/
The main focus of my lab is the neurobiology of drug addiction. Our aim is to identify molecular mechanisms that underlie the development and persistence of drug dependency with the long term aim of developing novel therapeutics for the treatment of drug relapse. We use zebrafish as our model system. The advantages of using zebrafish lie in the relative ease with which one can perform pharmacological and genetic screens in this species: The adults are easy to keep and breed with each pair laying up to 300 eggs in a single cross, fry can be grown in multiwell plates and drugs can be easily administered by addition to the water. Observations that zebrafish show conditioned place preference reward responses to common drugs of abuse, and that mutations that affect mesolimbic dopaminergic transmission (a central component of the reward pathway in humans) prevent drug-associated reward seeking in zebrafish, as in mammals, support the use of this model organism for the study of addiction. We have identified long lasting changes in gene expression in the brains of zebrafish withdrawn from chronic ethanol or nicotine treatment and demonstrated that zebrafish show drug-primed or stress-induced reinstatement of ethanol or nicotine-seeking. Using pharmacological manipulation of the pathways/receptors involved we are testing the hypothesis that the identified changes in gene expression reflect changes in neurotransmission which contribute to reinstatement of drug seeking. In addition we are using our conditioned place preference and reinstatement assays in a pilot genetic screen to identify factors that influence the establishment of ethanol dependence and stimulus-induced reinstatement of ethanol seeking.
A second field of study is the role of calcium signaling during development. This project is part of a long standing collaboration with Dr Rachel Ashworth. Here the focus is on the role of activity-generated calcium signals in muscle development. Dr Rachel Ashworth has established the temporal characteristics of activity dependent calcium signals during the initial stages of neuromuscular innervation. Variation in the dynamics of intracellular calcium signals (such as amplitude and duration) is a key mechanism by which downstream responses to calcium signalling are regulated. In muscle the pattern of nerve-mediated depolarisation influences expression of contractile proteins and nerve activity can influence the proportion of fibre types in mammalian skeletal muscle. The developmentally regulated variation in calcium dynamics shown by Dr Ashworth is consistent with nerve-mediated calcium signals directing specific components of slow muscle development. In collaboration with Dr Ashworth we are now examining the roles of specific components of the intracellular calcium machinery, including ryanodine receptors, in the control of this process.
Research group
Postgraduate supervision:
Baiamonte, Matteo; m.baiamonte ("at" sign) qmul.ac.uk;
Brock, Alistair; a.j.brock ("at" sign) qmul.ac.uk;
Parmar, Miralkumar; m.parmar ("at" sign) qmul.ac.uk;