11/23/2022
By Kwok Fan Chow

The Kennedy College of Science, Department of Chemistry, invites you to attend a research proposal defense by Subrata Chandra entitled “Physicochemical Investigation and Electrical Measurement of Biomolecular Interactions at the Single-molecule Level.” The defense will be held in Olney Hall, Room 520 on Tuesday, December 6 at 9:30 a.m.

Committee Chair:
Prof. Juan Artes Vivancos, Department of Chemistry, University of Massachusetts Lowell

Committee Members:
1) Prof. Dionysios Christodouleas Department of Chemistry, University of Massachusetts Lowell
2) Prof. Michael Ross, Department of Chemistry, University of Massachusetts Lowell
3) Prof. Marina Ruth, Department of Chemistry, University of Massachusetts Lowell


Abstract:

The dynamic interactions between biomolecules like proteins, nucleic acids, lipids, and their binding kinetics at a molecular level are exciting research domains and it has made considerable progress over the years. Comparing single-molecule results with the known behavior of the cellular interactions in bulk remains a challenge over the years. Understanding complex biological processes including long-range communications (like signaling, damage detection, and repair) and charge transport in biomolecules at the nanoscale are still underexplored. The quantitative biophysical study of these complex mechanisms can help to reveal the underlying molecular machinery inside the human cell. Analysis of those interactions at the molecular level can also help us in therapeutics. Characterization and measurement of such interactions can be done by various biochemical, electrical, biophysical, and computational methods. Mostly, here we will be focusing on electrical measurements to explain those phenomena.

Biomolecular electronics, the discipline studying the charge transfer process in biomolecules, has the potential to describe the interaction between electronic materials and biological systems (RNAs) at molecular interfaces. We use the Scanning tunneling microscope-assisted break junction method (STM-BJ) to study charge transport in short oligonucleotides by reproducible conductance histograms related to their biomolecular structure and conformations. Each biomolecule will be confined within a nanometric gap at a well-defined molecular orientation to measure its electrical properties. Herein, we measured, for the first time, the conductance of individual dsRNA molecules and compared it with the conductance of DNA: RNA hybrids. The average conductance values are similar for both biomolecules, but the distribution of conductance values shows an order of magnitude higher variability for dsRNA, indicating higher molecular flexibility of dsRNA. In our next study, we have demonstrated base-mediated charge transport in specific single-stranded 5 bp and 10 bp RNA oligonucleotide sequences. We found base stacking is the main factor for getting a probable conductance value for those spontaneously formed RNA oligonucleotide junctions.

These results pave the way for measuring various biomolecular interactions at a single-molecule level. In the future, we will measure the conductance of a protein (Argonaute)– RNA complex. This can give us a better understanding of the formation of the RISC (RNA-induced silencing complex) complex and allow the study of the thermodynamics and kinetics of regulation of gene expression at the individual complex level. Lastly, we can use these fundamental results for designing next-generation smart biomaterials and biosensors that may address improved biological performances and advanced health monitoring in the future.


All interested students and faculty members are invited to attend.