Ariel Alperstein
University of Delaware, DE·Biophysics
Certain proteins and protein fragments can misfold and clump together into fibers called amyloid, a process tied to Alzheimer's disease, diabetes, and cardiomyopathy, a disease of the heart muscle. Cells defend themselves with chaperone proteins, molecular minders that grab onto sticky peptides before they aggregate.
- Fields
Biophysics
Chemistry
Biochemistry
- Topics
two-dimensional infrared spectroscopy
super-resolution microscopy
vibrational spectroscopy
- Grants
- 1 known grant, through Feb 2030
What they work on
- Improve two-dimensional infrared microscopy in both space and time to build a super-resolution 2DIR microscope, extending an ultrafast vibrational method that reports protein backbone folding to finer spatial detail.
- Test whether the chaperone proteins HSP27 and αB-crystallin alter the aggregation and secondary structure of desmin peptide fragments, the muscle-protein pieces implicated in cardiomyopathy, using bulk 2DIR measurements.
- Pinpoint the specific peptide regions involved in chaperone contacts by labeling the backbone with carbon-13 and oxygen-18 isotopes to isolate the vibrational signal of individual regions or single amino acids.
- Map which chaperone domains change structure during protective contacts with desmin, using segmental carbon-13 labeling of HSP27 and αB-crystallin to read out domain-specific vibrations.
- Collect time-resolved 2DIR data that distinguishes the signal of an aggregating amyloid peptide from that of an added chaperone, establishing kinetic measurements of chaperone intervention.
More about the research
One complication is polymorphism: the same peptide can fold into more than one amyloid shape, and it is not known whether chaperones recognize these different shapes equally well. Answering that requires a measurement tool that can read out protein shape within a messy, mixed population of molecules — which is what this project sets out to build.
Why it matters
Understanding exactly how chaperone proteins grip amyloid-forming peptides, and whether different misfolded shapes are recognized differently, could guide the design of chaperone-fragment-based drugs for amyloid diseases, including the cardiomyopathy linked to desmin aggregation. The super-resolution infrared microscope being developed would also give biophysicists a general way to read protein structure inside heterogeneous samples.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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Pennsylvania State University, PA·Chemistry
Test whether the lifetimes of excited electronic states in atomically precise metal nanoclusters can control how their acoustic modes (whole-particle vibrations) are excited, using coherent multidimensional laser spectroscopy and theory.
Benjamin Partridge
University of Rochester, NY·Chemistry
Establish structure-function relationships for amphiphilic molecules that assemble into supramolecular capsules, linking molecular design to assembly and to how well they block amyloid beta fragments from forming fibers.
David Dettman
University of Arizona, AZ·Earth & Environmental Science
Expand a prototype TILDAS system, an infrared laser instrument that identifies molecules by the light they absorb, by adding a new laser unit to measure oxygen-17 in CO2.
The school
University of Delaware: 22 labs on PI Pages, $466M a year on research, 298 research doctorates a year.
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