Ett nytt cellskelett som en terapeutisk måltavla för behandling mot barncancer

This proposal addresses gaps in knowledge in the function of a novel discover cytoskeletal element formed by gamma (γ)-tubulin (TUBG), the γ-tubulin meshwork. Our ultimate goals are to elucidate the roles of TUBG in cellular homeostasis and disease development, and to translate all gained knowledge into the development of personalized life-enhancing medicines for children that target tumor cell proliferation and differentiation.
TUBG1 function is important in the architecture of the cortex in the developing brain and spontaneous mutations in the TUBG1 gene are associated with lissencephaly and microcephaly (brain malformations that can lead to mental retardation and neurological morbidity). My research focuses on the therapeutic targeting of TUBG1 and on the functional role of TUBG1 in brain development, neurodegenerative disorders and embryonal tumor formation. My work focuses on three protein groups: TUBG (TUBG1 and TUBG2), retinoblastoma 1 (RB1) and Ser/Thr SadB kinase family. TUBG1 is a ubiquitously expressed protein, whereas TUBG2 is expressed during the first stage of embryonic development (up to blastocyst stage), and in the brain. In the nucleus and cytoplasm, TUBG forms an interconnected cellular meshwork, the γ-tubulin meshwork, which is composed of centrosomes, γ-tubules and γ-strings. The γ-tubulin meshwork regulates cell proliferation and homeostasis. We hypothesize that the activity of TUBG2 is necessary for lineage progression of NSC to neurons and glia, whereas TUBG1 regulates the proliferative rate of the differentiating neuron and glia. We are performing basic research and developing the necessary tools to target the activities of TUBG and SadB kinases in patients with neurodegenerative disorders.