by ARSACS | Apr 2, 2016 | Research in 2016
The research project has three specific objectives: to test the distribution of mitochondria in distal dendritic branches of Sacs primary PCs; to evaluate dysregulation of Ca2+ homeostasis in Sacs mice and finally to test the efficacy of targeted therapy in Sacs mice....
by ARSACS | Apr 2, 2016 | Research in 2016
Aim 1- Mapping GI network of ARSACS-associated SACS target using CRISPR 1.1. Quantitative readout for scoring GIs 1.2. GI validation and benchmarking Aim 2 – Characterizing ARSACS-linked SACS pathways for function discovery Duration: one year Grant: $100,000...
by ARSACS | Apr 2, 2016 | Research in 2016
Aim 1. Generate and characterize mice with chemically inducible mitochondrial division in Purkinje neurons (L7-CIDR mice). Aim 2. Evaluate rescue of Purkinje cell degeneration and motor deficits in SACS-/- mice by inducible mitochondrial division. Duration: two years...
by ARSACS | Apr 2, 2016 | Research in 2016
Objective 1. To generate in vitro disease model by creating ARSACS disease- specific cerebellar cells via iPSC from patients and healthy individuals as controls which will serve as a tool to depict disease-specific molecular markers. Objective 2. The comparative...
by ARSACS | Apr 2, 2016 | Research in 2016
The objective is to identify compounds that will improve axonal transport in neurons carrying the mutation. The compounds we will survey are ones with a known mechanism of action and thus will identify cellular signaling pathways with the potential to overcome the...
by ARSACS | Apr 2, 2016 | Research in 2016
The research project is to examine the ARSACS mutations in the J-HEPN fragment of sacsin, to engineer Hsc70 to potentially identify sacsin-directed substratesand to address whether sacsin promotes degradation of neurofilament heavy subunit (NFH) Duration: one year...
by ARSACS | Apr 2, 2016 | Research in 2016
The greatest bottleneck in structural studies of Sacsin is the preparation and screening of fragments of thousands of Sacsin constructs with different boundaries, different mutations, and sequences from different species. To overcome this, we have developed a...
by ARSACS | Apr 2, 2016 | Research in 2016
The researchers will use genome editing of hiPSCs to test the hypothesis that point mutations in the SACS gene lead to alterations in mitochondrial function and neurofilament organization in neurons derived from ARSACS patients. Specific aim 1: Generate genome-edited...
by ARSACS | Apr 2, 2016 | Research in 2016
The overall objective of the project is to devel+op TPS-100 as a first treatment of ARSACS and to identify a second generation drug based on efficacy and knowledge of receptor pharmacology of TPS-100. Our goal is to synthesize a directed library of compounds with...
by ARSACS | Mar 29, 2016 | Research in 2016
The McKinney and Watt labs, which are located in close proximity in the Bellini Life Sciences Complex and who already share a mouse colony of ARSACS mice (Sacs-/-) will determine the physiological mode of action of TPS-100 a pharma and aminopyridines on Purkinje cell...
by ARSACS | Mar 28, 2016 | Research in 2016
Continue the investigation of sacsin partners using the BioID assay, using the full length sacsin as well as different sacsin mutants and to further characterize ARSACS fibroblast cytoskeletal disorganization as a cell-based model. Duration: one year Grant: $100,000...
by ARSACS | Mar 28, 2016 | Research in 2016
The research project has two specific aims: to continue experiments to determine if loss of sacsin functions in NF metabolism plays a central role in pathogenesis of ARSACS and to determine the effect of sacsin domains on the phenotype in our ARSACS culture models and...
