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Jan TonnessenOptogenetic control of epileptiform activity in vitro - how to make cells not too exciting

Abstract :


The presentation covers work of my PhD thesis, demonstrating that by virally introducing an orange light-driven inward chloride pump to the cell membrane of hippocampal neurons in mouse organotypic slice cultures, we can decrease the duration of induced epileptiform activity to less than half of controls, simply by applying orange light to our preparation.

Application for available post-doc positions in the neuroscience field.
I am currently in the late phase of my doctoral studies and planning to defend my PhD thesis from Lund University, Sweden, on March 13th 2010. Shortly hereafter I desire to commence post-doctoral studies to continue my career as a research professional. I feel the post-doc period is a good and natural opportunity to go to a laboratory abroad, and to engage in new projects. As my girlfriend has recently started a post-doc position in the group of Jérôme Baufreton at the Laboratoire Mouvement – Adaptation – Cognition, Université Victor Segalen Bordeaux 2, I am looking for positions in, or near, Bordeaux.

Through the last 4.5 years I have been a doctoral student at the Experimental Epilepsy Group/Division of Neurology at Lund University in Sweden, in the group of prof. Merab Kokaia under prof. Olle Lindvall’s Section of Restorative Neurology. The first 3 years were funded through a EU 6th Frame Program, Marie Curie Early Stage Training Fellowship. My thesis work relates to optogenetic gene therapy in epilepsy, and neural stem cell therapy for Parkinson’s disease. The experimental work is based predominantly on electrophysiological patch-clamp measurements from stem cell cultures, acute brain slices as well as organotypic cultures of brain slices, and I have acquired great expertise in patch-clamp techniques, including whole-cell, perforated patch and field recordings. In addition, I have combined patch-clamping with amperometric carbon µ-fiber electrode measurements of dopamine exocytosis, with electrical field stimulations and with Pico-spritzer drug application. Another important technique I have established and used extensively, in conjunction with electrophysiology, is optogenetic cell control, using halorhodopsin (NpHR) to control neurons optically in acute and cultured slices. Through my experiments I acquired expert knowledge on acute and organotypic slice cultures, primary neural and stem cell cultures, stereotaxic injections/transplantations, immunohistochemistry and several other techniques. In addition, I am involved in developing lab-on-a-chip technologies, integrating nano-electrodes and µ-analysis tools in perfusion platforms for online cell and slice culturing and monitoring (see www.excell.nu).
Before enrolling my self in the 4-year PhD program at Lund University I have conducted experimental work, and published, in other neuroscience fields, including endogenous morphine, applying HPLC to disclose its synthesis and role in species ranging from invertebrates to humans; cerebral blood-flow and sub-arachnoid hemorrhage in rats, comparing two experimentally challenging methods by simultaneous application: laser Doppler flowmetry and the intra-arterial 133Xenon injection method.
As I am conducting my doctoral thesis in Sweden and have previosly spent one semester at the Neuroscience Research Institute at State University of New York, SUNY, College at Old Westbury, under Dr George B. Stefano, I already have experience in adapting to international laboratories.
By currently participating actively in 2 EU FP7 consortiums (NeuroStemCell and Excell) I am familiar with participating in large international multi-disciplinary projects.
Though my current strength is within epilepsy, Parkinson’s disease, electrophysiology, optogenetics, stem cells and organotypic cultures I am also open to perusing new challenges in other fields pertaining to neurobiological and medical sciences.

 

Selected publications

Tønnesen J, Sørensen AT, Deisseroth K, Lundberg C, Kokaia M. Optogenetic control of epileptiform activity. Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12162-7.

Clare L Parish, Gonçalo Castelo-Branco, Nina Rawal, Jan Tonnesen, Andreas Toft Sorensen, Merab Kokaia, Olle Lindvall and Ernest Arenas. Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice. J Clin Invest. 2008 Jan;118(1):149-60.

Tonnesen J, Pryds A, Larsen EH, Paulson OB, Hauerberg J, Knudsen GM. Laser Doppler flowmetry is valid for measurement of cerebral blood flow autoregulation lower limit in rats. Exp Physiol. 2005 May;90(3):349-55.

Pryds A, Tonnesen J, Pryds O, Knudsen GM, Greisen G. Cerebral pressure autoregulation and vasoreactivity in the newborn rat. Pediatr Res. 2005 Feb;57(2):294-8.