Spencer A. Shorkey

ORCID: 0000-0002-7502-6980
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About
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Research Areas
  • Nanopore and Nanochannel Transport Studies
  • Advanced biosensing and bioanalysis techniques
  • Lipid Membrane Structure and Behavior
  • DNA and Biological Computing
  • Microfluidic and Capillary Electrophoresis Applications
  • Advanced Nanomaterials in Catalysis
  • RNA modifications and cancer
  • Analytical Chemistry and Sensors
  • Autophagy in Disease and Therapy
  • RNA Interference and Gene Delivery
  • Nanocluster Synthesis and Applications
  • Mosquito-borne diseases and control

University of Massachusetts Amherst
2017-2024

Amherst College
2017

DNA is a promising next-generation data storage medium, but challenges remain with synthesis costs and recording latency. Here, we describe prototype of system that uses an extended molecular alphabet combining natural chemically modified nucleotides. Our results show MspA nanopores can discriminate different combinations ordered sequences nucleotides in custom-designed oligomers. We further demonstrate single-molecule sequencing the using neural network architecture classifies raw current...

10.1021/acs.nanolett.1c04203 article EN cc-by-nc-nd Nano Letters 2022-02-25

Conformational changes of proteins are essential to their functions. Yet it remains challenging measure the amplitudes and time scales protein motions. Here we show that cytolysin A (ClyA) nanopore was used as a molecular tweezer trap single maltose-binding (MBP) within its lumen, which allows conformation be monitored electrical current fluctuations in real time. In contrast two state binding model, measurements revealed three distinct ligand-bound states for MBP presence reducing...

10.1021/acsnano.9b07385 article EN ACS Nano 2020-01-29

Abstract Covalently attaching ubiquitin (Ub) to cellular proteins as a post‐translational modification can result in altered function of modified proteins. Enzymes regulating Ub modification, such ligases and deubiquitinases, are challenging characterize part due the low throughput in‐vitro assays. Single‐molecule nanopore based assays have advantage detecting with high specificity resolution, label‐free, real‐time fashion. Here we demonstrate use MspA for discriminating quantifying We...

10.1002/cbic.202100092 article EN ChemBioChem 2021-06-01

The flaviviral NS2B/NS3 protease is a conserved enzyme required for flavivirus replication. Its highly dynamic conformation poses major challenges but also offers opportunities antiviral inhibition. Here, we established nanopore tweezers-based platform to monitor conformational dynamics in real-time. Molecular simulations coupled with electrophysiology revealed that the could be captured middle of ClyA lumen, stabilized mainly by electrostatic interactions. We designed new

10.1101/2024.05.14.594247 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2024-05-15

DNA is a promising next-generation data storage medium, but the recording latency and synthesis cost of oligos using four natural nucleotides remain high. Here, we describe an improved DNA-based system that uses extended 11-letter molecular alphabet combining chemically modified nucleotides. Our extended-alphabet paradigm offers nearly two-fold increase in density potentially same order reduction time. Experimental results involving library 77 custom-designed hybrid sequences reveal one can...

10.1101/2021.09.27.462049 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2021-09-28

Ubiquitination plays a prominent role in cell signaling networks. Enzymes governing ubiquitination include the conjugation machinery along with deconjugating enzymes - deubiquitases. A MspA nanopore is demonstrated as sensor for discriminating and quantifying various ubiquitin proteins. Real-time measurement of polymeric chain disassembly by deubiquitinating enzyme was performed kinetics were determined. The implementation into arrays could enable high throughput characterizations unknown...

10.1002/cbic.202100345 article EN ChemBioChem 2021-07-24
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