Creating tools to make experimental biochemistry accessible to people with blindness

Project summary. People with blindness and low vision (BLV) experience systemic exclusion from biomedical science because the tools of experimental science—and the data they produce—are inaccessible. The two central hypotheses of this proposal are: (i) the tools and information of an experimental biomolecular research lab can be made accessible to people with BLV with interventions that incorporate universal design, and (ii) persons with BLV can use these tools to test biomedical hypotheses and publish their results in peer-reviewed journals. This project has four aims; two aims for developing assistive technology, and two aims to use this technology to test hypotheses about (i) heteromeric interactions between wild-type (WT) Cu, Zn superoxide dismutase (SOD1) and mutant forms of SOD1 that cause amyotrophic lateral sclerosis (ALS), and (ii) redox properties of mitochondrial redox enzymes. In aim 1, we plan to methodically make each tool/technique in the PI’s lab accessible, beginning with SDS-PAGE and Western blotting, protein purification, capillary electrophoresis, PCR, and touch screen devices (pH meters, centrifuges). Assistive technology is being designed and 3D printed in the PI’s lab, including a device that enables researchers with total blindness to autonomously load SDS-PAGE gels by hand. Robotic devices that weigh solids and initiate biochemical reactions are also being made accessible. In aim 2, graphical imagery and data (electropherograms, spectra, electron micrographs) are converted into lithophanes (engravings that provide tactile readouts and optical readouts via light scattering). Haptic gloves—developed for gaming—will be adapted to help researchers with blindness visualize virtual objects (protein structures, CAD files, etc.). In aim 3, these tools will be used by blind and sighted researchers to test how incorporation of WT SOD1 into fibrillar mutant SOD1 affects its kinetic, thermodynamic, and structural properties. Here, fluorescence spectroscopy, amide H/D exchange, chemical crosslinking and cryo-electron microscopy will be used to test the hypothesis that WT SOD1 incorporates into mutant fibrils to alter their structure/morphology, stability and propagation rate. In aim 4, “protein charge ladders,” capillary electrophoresis, and site directed mutagenesis will be used to test the hypothesis that long-range electrostatic interactions in mitochondrial metalloproteins play a dominant role in controlling their redox properties. Each aim is developed for (and in collaboration with) faculty and researchers who have early blindness and persons with late blindness, who developed blindness as adults after Ph.D. training in biomedical science (these latter persons have been forced to drop out of science). This project involves a collaborative team of sighted and blind biochemists, chemists, electron microscopists, and computer scientists, including undergraduate, post- doctoral, and independent scientists with blindness currently in the PI’s lab.