In situ Lysosomal Ion Imaging as a Sensitive Diagnostic for Lysosomal Disorders

Type of Award: catalyst
Award Number:
Award Period: March 2018 - February 2020
Amount Awarded: $ 250,000.00
PI(s): Yamuna Krishnan, PhD, UChicago; Dimitri Krainc, PhD, NU;

Abstract: We propose to develop a diagnostic for lysosomal function with possible application in lysosomal disorders. The lysosomal pathway integrates important cellular processes in all cell types, but finds particular importance in supporting the unique physiological demands of neurons. There is a preponderance of disease-causing and risk genes for various neurological disorders, including over 60 lysosomal storage disorders. These genes have predicted sites of action within the lysosomal pathway, suggesting that disruption of lysosomal function plays a key role in these disorders. However, it has not yet been possible to measure lysosomal function with current techniques in human tissues. Here, we propose to develop an ultrasensitive diagnostic that works by measuring lysosomal integrity, and thereby function, in easily accessible cells derived from blood draws. This approach will be suitable for high throughput platforms, with potential application in clinical trials where lysosomal function could be used as a readout of therapeutic intervention.