The University of Sheffield
Department of Biomedical Science

Project Title: Molecular mechanism of Lowe Syndrome

Supervisor: Dr. Kai Erdmann
(Dr Erdmann joins the University of Sheffield in summer 2012 and the following project will be based at the department of Biomedical Science)

Project Description:

Lowe syndrome is a X-linked disease characterised by congenital cataracts, mental retardation and reabsorbtion defects in kidney. To learn more about this devastating disease, please go to the Lowe syndrome trust website: http://www.lowetrust.com

Mutations in the gene for the phosphatidylinositol-5-phosphatase OCRL1 are responsible for the observed defects in Lowe syndrome, however the molecular understanding of Lowe syndrome is sparse and a cure currently does not exist. OCRL1 is a Rab effector protein involved in vesicular trafficking and likely also in cellular signaling. Recently, we have identified new interacting proteins for OCRL1 and described a potential role of OCRL1 in the regulation of endocytosis.

The goal of this project is to further characterise the protein network OCRL1 is part of. Novel interacting proteins will be analysed using cell biological and biochemical methods. Finally, the contribution of these novel interacting proteins to the patho-cell biology of Lowe syndrome will be evaluated using several in vitro cell culture systems.

References:

  1. Erdmann, K.S., Mao, Y., McCrea, H.J., Zoncu, R., Lee, S.Y., Summer, P., Modregger, J., Biemesderfer, D., Toomre, D., and De Camilli, P.
    A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway.
    Dev. Cell, 13, 377-390 (2007)
  2. Schurman, S.J., and Scheinman, S.J.
    Inherited cerebrorenal syndromes.
    Nat. Rev.Nephrol., 529-538 (2009)
  3. Hou, X., Hagemann, N., Schoebel, S., Blankenfeldt, W., Goody, R.S., Erdmann, K.S.,  Itzen, A.
    A structural basis for Lowe syndrome caused by mutations in the Rab binding domain of OCRL1.
    EMBO J., 30, 1659-1670 (2011)

Contact Details:

Dr. Kai Erdmann

Web:

Email: kai.erdmann@rub.de