The regulation of SMN function in SMA.
Principal investigator(s) :
Dr. Olga Tapia,Institution :
University of Cantabria - SpainGrant :
€ 40,000Grant Type:
FellowshipCall number :
8Start year :
2016Duration :
1 yearStatus :
EndedWhile the role of SMN in the biogenesis of snRNPs has been studied extensively over the past 20 years, very little is known about the regulation of SMN functions by post-translational modifications (PTMs). In particular, the impact of PTMs of SMN on its interactions, protein stability and subcellular localisation. The identity of signaling pathways controlling SMN function in snRNP assembly remains a key question in the field and their elucidation has potential to open novel therapeutic avenues for the treatment of SMA.
What are the researchers aiming to do?
Dr. Tapia will seek to understand the regulation of SMN function by PTMs and their implication in the molecular pathophysiology of SMA.
How will the researchers do this?
Dr. Tapia will seek to see if the acetylation induced with HDAC inhibitors, nowadays used in SMA therapy, has any impact on SMN PTMs and functional regulation of the protein. In particular, they will determine whether the acetylation state of SMN impacts on its subcellular localization, interactions and stability, as well as on CB biogenesis, assembly of the splicing machinery and transcriptional activity. They will use cultured cells and mouse spinal cord motor neurons, the main target of reduced SMN function in human neuropathology.
About Dr. Tapia
Dr. Olga Tapia is a senior post-doctoral scientist at the laboratory of "Cell Biology of the Nucleus" at the University of Cantabria-IDIVAL in Santander (Spain).