The Weiss laboratory invents new chemical tools to interrogate biology at the level of atoms and bonds. Many projects in the lab apply phage display to evolve peptides and proteins to bind cancer and diabetes-associated biomarkers. The resultant viruses with the disease-specific ligands have been directly wired into electrical circuits for measurement of disease marker levels in urine through collaboration with Prof. Reg Penner (UCI, Department of Chemistry). During the COVID era, our two laboratories focused 100% on the development of a new generation of COVID diagnostics. This research led to the identification of a prognostic antibody associated with severe COVID-19 disease outcomes. Patients with this antibody present with the molecular signature of antigenic original sin, in which an earlier infection predisposes the patient to synthesize ineffective antibodies. The source of this earlier infection was unexpected, dating back to 2014.
Scaling down to the single molecule level, the lab collaborates with Prof. Phil Collins (UCI, Department of Physics and Astronomy) to directly wire individual enzymes into carbon nanotube-based electronic circuits, which can record the sound made by the enzymes in motion. The approach expands what’s possible for dissecting enzymes, in terms of duration of observation (weeks), time resolution, (microseconds), and temperature tolerance (up to Taq DNA polymerase’s native temperatures). The results from the two projects uncover molecular mechanisms required for biology’s most important processes – DNA replication and the immune response to a rampaging pandemic.
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