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UCL Division of Biosciences

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Dr Anselm Zdebik

Dr Anselm Zdebik

Associate Professor

Neuro, Physiology & Pharmacology

Div of Biosciences

Joined UCL
1st Oct 2007

Research summary

Past research was focused on mammalian CLC proteins, and we discovered that several mammalian family members are 2Cl-/H+ antiporters rather than chloride channels, and identified key residues for proton transport as well as the basis for nitrate selectivity of some plant CLC proteins.

Current research is looking at the pathophysiological consequences of mutations in KCNJ10, an inwardly rectifying potassium channel. Loss of function in both homomeric mutant and heteromeric mutant KCNJ10/16 potassium channels results in EAST syndrome, characterized by Epilepsy, Ataxia, Sensorineural hearing loss and mild renal salt wasting (Tubulopathy). We identified altered open probability, impaired PIP2 binding and altered pH dependence in some mutations.

Several patients with mutations in KCNJ10 have more recently been described which do not display the typical symptoms of EAST syndrome. In one case, we found that CNS and hearing is spared because the particular mutation is affecting heteromeric channels severely, but leads to relatively mild loss of function in homotetrameric channels. We are currently working on other mutations leading to partial EAST syndrome, using mainly electrophysiological techniques such as two-electrode voltage clamping and biochemical assays to assess membrane abundance as well as single channel recordings to directly investigate the effect of mutations. We also use molecular modelling to understand the impact of new mutations by comparison with other known hotspots. We also study mutations on a single-channel level, which allows to "see" a single ion channel live in action, in real time.

Apart from Xenopus oocytes, we also use zebrafish models to investigate seizures and neurodegeneration due to EAST syndrome mutations as well as neuronal ceroid lipofuscinoses, and we have a long-standing collaboration with Claire Russell on these studies, which we have now expanded to look at electroretinograms as well. Mutations in CLN3 lead to early-onset blindness in children, and studying zebrafish allows to identify potentially therapeutic compounds.

Teaching summary

Physiology at Freiburg, Hamburg, Berlin (Max-Delbruck Centre). Since 2008 Lecturer, Neuroscience, Physiology and Pharmacology, UCL

Education

Other Postgraduate qualification (including professional), ATQ07 - Holder of a PGCE in higher education, secondary edu, further edu, life long lear |
Other Postgraduate qualification (including professional), ATQ01 - Successfully completed an institutional provision in teaching in the HE sector |
Other Postgraduate qualification (including professional), ATQ02 - Recognised by the HEA as an Associate Fellow |
Ruprecht-Karls-Universitat Heidelberg
Other higher degree, Master of Education | 1998

Biography

Medical education in Heidelberg, PhD in 1998, MD 2000
Clinical training at Freiburg University Hospital (Gastroenterology, Infectious diseases)
Physiology Freiburg University
2000-2008 Postdoc with Thomas J. Jentsch, Hamburg and Berlin

Since 2008 Lecturer, then Senior Lecturer at UCL

Publications