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- Professor of Pharmacology
- Neuro, Physiology & Pharmacology
- Div of Biosciences
- Faculty of Life Sciences
We work at understanding the functioning of receptors that mediate fast synaptic transmission, and focus on two classes of ion channels in the nicotinic superfamily, nicotinic and glycine receptors. Different types of nicotinic receptors (which are all excitatory and activated by the transmitter acetylcholine) mediate the initiation of muscle contraction by the peripheral terminals of motor neurones in the spinal cord and the regulation of involuntary bodily functions, such as blood pressure at the level of autonomic ganglia. Yet other forms of nicotinic receptors are present in the brain and are affected by the nicotine in tobacco smoke. Glycine receptors are activated by the simplest amino acid, glycine, and are inhibitory, acting to dampen excessive neuronal activity, particularly in the lower levels of the central nervous system, such as the spinal cord. For instance, without glycine transmission there would be no coordination between muscles that have opposite effects on the movement of a limb. In man, inherited mutations in nicotinic or glycine receptors are known to produce neurological disease. Our general aim is to understand in quantitative terms how a receptor functions as a one-molecule machine. This is only possible because, thanks to the techniques of patch clamp and single channel recording, the activity of a single receptor molecule can be seen in real time. This type of work is important not just for neuroscience (i.e. for understanding synaptic transmission), but also for pharmacology. Indeed, to this day concepts that are central to pharmacology and receptor theory, such as partial agonism and efficacy, are well understood (i.e. can be quantitatively formulated) only for receptors that belong to the ligand-gated ion channel class (largely because of past research in this department). Some of the questions being investigated include: * How do differences in the properties of the several types of receptors derive from differences in the sort of protein subunits that make them up (each of which is produced by a different gene)? * How does the binding of the transmitter to the receptor result in channel opening and what portions of the subunits are important in this process? * How many molecules of transmitter need to bind for the channel to open efficiently? * How do disease mutations in the amino acid sequence of subunits impair the working of the receptor? A combination of electrophysiological recording and molecular biology techniques are used in the laboratory in order to obtain in cell cultures or in Xenopus oocytes receptors that are similar to those in the brain of humans and animals. We then record the electrical currents they produce both in their normal form and in forms that have been mutated. While a range of electrophysiological recording techniques are in everyday use in the laboratory, a strong focus is on single channel recording and its interpretation.
I contribute to Pharmacology courses for science students, PHAR2002/5 General and Systematic Pharmacology (lectures, tutorials, coursework) and PHAR2003 Experimental Pharmacology (seminars, tutorials); I am in charge of the "Unknown Drug" Project practicals in the second half of this course, where teams of students identify an adrenergic drug by designing and carrying out wet lab experiments (lecture, tutorials, practicals, coursework)
I offer research projects in my lab to undergraduates (PHAR3010) and postgraduates (MSc Neuroscience, rotation PhD students)
Together with David Colquhoun, I organise a summer course. This is a week-long intensive workshop on the principles of Understanding ion channels in terms of mechanisms, aimed at postgraduates and postdoctoral researchers in this research area.
|1988||PhD||Doctor of Philosophy – Pharmacology||St Bartholomews Hospital|
|1983||Spec||Specializzazione – Experimental Pharmacology||Universita degli Studi di Milano|
|1981||BSc||Bachelor of Science – Pharmaceutical Chemistry||Universita degli Studi di Ferrara|