02/18/2026
By Kwok Fan Chow

The Kennedy College of Science, Department of Chemistry, invites you to attend a Ph.D. Research Proposal defense by Gayan Kanchana Aluthwala Acharige entitled “Mechanistic Study of Trehalose-Directed Nanoparticle Internalization in Mycobacteria.”

Date: Thursday, March 5, 2026
Time: 2 p.m.
Location: Olney, Room 520

Committee:

  • Advisor: Mingdi Yan, Department of Chemistry, University of Massachusetts Lowell
  • Matthew Gage, Department of Chemistry, University of Massachusetts Lowell
  • Olof Ramstrom, Department of Chemistry, University of Massachusetts Lowell
  • Pengyuan Liu, Department of Chemistry, University of Massachusetts Lowell

Abstract:
Nanoparticles are commonly functionalized with surface ligands to promote selective interactions with biological systems; however, the molecular mechanisms that enable bacteria to recognize, uptake and transport ligand-functionalized nanoparticles remain largely undefined. From the previous studies it has been shown that trehalose-functionalized nanoparticles can be selectively internalized by mycobacteria. Trehalose is a disaccharide essential for the survival and pathogenicity of mycobacteria, but it is absent in mammalian biology. This makes trehalose-utilizing proteins in mycobacteria attractive antibiotic targets.

Our main goal of this work is to understand the trehalose-mediated nanoparticle uptake, transportation and their interactions at molecular level. To achieve this, we developed magnetic photoaffinity probes (MAPs) functionalized with trehalose and the photoaffinity labeling agent, perfluorophenyl azide (PFPA). Iron oxide magnetic nanoparticles are selected because they enable straightforward synthesis, efficient surface functionalization, and, most importantly, efficient magnetic separation of covalently captured proteins. PFPA is selected due to its ability to reduce ring expansion reaction of phenyl azide, ease of synthesis, excellent storage stability, and high reactivity towards photoirradiation. In this project, ligand ratio and density will be systematically varied to optimize multivalent binding, maximize specific protein capture and minimize non-specific adsorption.

Iron oxide magnetic nanoparticles were synthesized by thermal decomposition and subsequently functionalized with thiol groups using (3-mercaptopropyl)trimethoxysilane. Trehalose and PFPA derivatives were synthesized through multistep synthetic sequence. They were conjugated to thiolated iron oxide nanoparticles via disulfide exchange chemistry. Future work will include protein photocrosslinking experiments in mycobacteria, followed by magnetic separation of covalently captured proteins. These proteins will then be released by disulfide cleavage and identified using liquid chromatography-tandem mass spectrometry.

All interested students and faculty members are invited to attend.