In September 2007 I joined the Netherlands Institute for Neurosciences in the department Retinal Signal Processing as a PhD student to study the functions of connexin proteins.
The human eye, actually a part of the brain, detects our visual world with about 100 million sensors: the rods and cones. After reaching these sensors, this visual information is subsequently processed by several neural cell layers so that all information can be sent to the brain through no more than 1 million nerves. This means that all visual information falling onto the retina has to be compressed by at least 100 times!
Part of the retinal processing of the visual input is established by feedback from horizontal cells to cones. In this process connexins are believed to play a very important role, through a mechanism called ephaptic feedback.
Connexins are proteins that were originally discovered to make up gap junctions, channels between two adjacent cells. Also, connexins can form hemichannels, 'half gap junctions', which participate in the release of small molecules and cell volume control.
Currently, there is a scientific debate on the possible roles of hemichannels in feedback. The debate revolves around questions concerning calcium currents and pH sensitivity in the synaptic complex between cones and horizontal cells in the retina.
In my PhD study I aim to uncover the underlying molecular mechanisms and properties that determine connexin function. To this end, both wild-type connexins and mutant dominant negative connexins will be analyzed through various expression systems such as the African clawed frog eggs (Xenopus laevis oocytes) and mouse neuroblastoma (N2a) cell cultures. On these systems I will perform imaging studies in addition to current recording and patch-clamp experiments to gain insight in the biophysical properties of connexins.
Furthermore, transgenic zebrafish (Danio rerio) will be created containing the dominant negative mutations in the connexins, specifically those expressed in the retinal horizontal cells. These fish will express connexin proteins with altered or no functionality. This will presumably lead to a disrupted retinal processing. The biophysical characterization of the connexins and their dominant negative mutants will be extremely helpful in understanding the mechanisms leading to phenotypes of these fish and explaining the differences in retinal processing of these fish.
About me
At the Hogeschool Leiden I obtained the degree Bachelor of Applied Sciences (B AS) in Molecular Biology through the program 'Biology and Medical Laboratory Research' in 2004. Through an internship at the Academic Medical Center, Amsterdam at the lab for Genetic Metabolic Disorders, headed by prof. J.A. Wanders I became highly interested in the molecular workings of the brain that shape our behaviour.
To enhance my molecular skills and gain knowledge about the brain, I enrolled in the Master of Neurosciences program at the Vrije Universiteit Amsterdam, a program highly oriented towards proteomics and genomics. My graduation thesis was carried out under supervision of Carla V. Rothlin and Tal Burstyn-Cohen in the Molecular Neurobiology Lab, headed by Greg Lemke at the Salk Institute for Biological Studies in La Jolla, California, USA. I obtained my master's degree in August 2007.