Research Group of Prof. Dr. Sigrid Hoyer-Fender
I. Formation of the centrosome and the primary cilium
The centrosome is the main microtubule organizing center (MTOC) of the animal cell, located at the cell center at the vicinity of the nucleus. Important not only for the cytoskeletal architecture, for cell shape and cell motility, but moreover for ordered localisation of organelles, i.e. the Golgi apparatus. The centrosome in addition organises the mitotic spindle apparatus and is therefore important for chromosome segregation and maintaining life through generations. Very recently, the centrosome has come into focus as a cellular organelle involved in cell cycle progression and cytokinesis. A huge amount of centrosomal proteins have already been described but their functions are mostly unknown.
The centrosome of the animal cell consists of two centrioles surrounded by a pericentriolar matrix (PCM). Although mainly built of tubulin, both centrioles of a centrosome are functionally and structurally unequivalent. The older or mother centriole is characterized by the presence of appendages that are formed during cell cycle progression. Moreover, when cells escape the cell cycle the mother centriole eventually give rise to the basal body that outgrows a primary cilium. The primary cilium is found on most cells of the adult body and functions as a sensory organelle. Disturbances of primary cilia underly a lot of human diseases, e.g. kidney diseases, left-right axes formation and hydrocephalus. We are interested specifically in proteins of the appendages that are important for formation of primary cilia. The main questions we are asking are:
1. Which proteins interact in formation of the appendages and the primary cilium and what is their cellular function.
2. How are genes encoding centrosomal and ciliary proteins regulated at the transcriptional level.
3. Is there a cell cycle dependent transcriptional regulation of those genes.
4. Is deregulated expression of those genes involved in tumour progression.
5. How is the centrosome linked to the nucleus.