PRO RETINA Retinitis-Pigmentosa-Price 2015
26. October 2015
This years Retinitis-Pigmentosa-Price was awarded to Dr. Karsten Boldt from the Institute for Ophthalmic Research for his work on the molecular mechanisms of Lebers congenital amaurosis (LCA5), a severe form of early childhood blindness.
To unravel the molecular basis of LCA5, Karsten Boldt analyzed how mutations in the LCA5 protein lebercilin affect ist function on the level of protein interactions. In photoreceptors, lebercilin is uniquely localized at the interconnecting cilium that connects the inner- with the the light receptive outer segments. Besides structurally bridging inner and outer segment, the cilium acts as a transport belt maintaining outer segment formation and integrity.
Karsten Boldt could show, that mutations of lebercilin impair the interaction of this protein to the intraflagellar transport (IFT) complexes. In collaboration with Ronald Roepman’s group in Nijmegen, Patsy Nishina's group in Bar Harbor, USA and Uwe Wolfrum’s group in Mainz, Karsten and his co-workers could demonstrate that loss of the Lebercilin-IFT connection leads to outer segment degeneration and thereby blindness. Karsten's work has been one of the first studies, describing pathological mechanisms on the level of protein complexes (Boldt et al, JCI, 2011).
By combining a biochemical with a computational approaches to analyse the modularity of protein complexes, Karsten Boldt could propose a modular design of the Lebercilin/IFT complex, which is likely to act as a small molecular machine for selection and transport of cargo to the outer segments (Texier et al, 2014, MCP).
The detailed description of Lebercilin's function and the consequences of its dysfunction in this severe form of childhood blindness is a prerequisite for the development of therapeutic approaches like gene therapy.
The price is founded by PRO RETINA Deutschland e.V.
For further information see: http://www.dog.org/?cat=226
- Boldt K, Mans DA, Won J, van Reeuwijk J, Vogt A, Kinkl N, Letteboer SJF, Hicks WL, Hurd RE, Naggert JK, Texier Y, den Hollander AI, Koenekoop RK, Bennett J, Cremers FP, Gloeckner CJ, Nishina PM, Roepman R, Marius Ueffing (2011). Disruption of intraflagellar protein transport in photoreceptor cilia causes Leber congenital amaurosis in humans and mice. Journal of Clinical Investigation. 121: 2169-80
- Texier Y, Toedt G, Gorza M, Mans DA, van Reeuwijk J, Horn N, Willer J, Katsanis N, Roepman R, Gibson TJ, Ueffing M, Boldt K. (2014) EPASIS: Elution profile analysis of SDS-induced sub-complexes by quantitative mass spectrometry. Molecular and Cellular Proteomics 13:1382-91