Postdoctoral Fellow for Single-molecule Studies of mRNA Loading on Nanoparticles

ScopeSys

Summary

The Leslie Single-molecule Biophysics Laboratory at UBC is looking for an exceptional PhD scientist to apply a new biophysical technique to the development of drug-delivery vehicles for oligonucleotide therapeutics.  The research project will focus on developing a new application of CLiC single-molecule imaging technology to simultaneously measure the size and mRNA cargo loading of lipid nanoparticles (LNPs).  The successful candidate will join a fast-paced interdisciplinary team of scientists and engineers working in the newly built Leslie Lab at UBC’s Michael Smith Labs, in collaboration with the Nanomedicine Innovation Network (NMIN) and our industry partner ScopeSys Inc.  Applicants should have a strong interest in pioneering new biophysical techniques and measurement capabilities, and establishing a career in biotechnology.

Qualifications

PhD required.  The successful candidate will be a well-organized, enthusiastic team player with excellent communication skills, who enjoys lab work, creative trouble-shooting, and who isn’t afraid of trying new things.  Although the position is based in an academic research lab, the research will be heavily driven by real and immediate problems in the development of novel nanomedicines and there will be a commensurate emphasis on developing solutions that are proven, robust, and ready for use by external collaborators and industry.

Developing a new single-molecule application or assay is a complex undertaking and this project will require an interdisciplinary skill set, combining physical, chemical and biological expertise. The ideal candidate will possess experience and interest in many of the following areas:

Physics and chemistry:

  • Nanoparticle engineering and characterization
  • Single-molecule biophysics
  • Optics and electronics
  • Surface science and chemistry

Biochemistry and molecular biology:

  • Design and structural analysis of DNA/RNA oligomers
  • Lipid and micelle interactions with oligonucleotides
  • Nanomedicine and oligonucleotide therapeutics

Instrumentation:

  • Single-molecule fluorescence microscopy – wide field and confocal
  • Biophysical assay and protocol development
  • Micro/nano-fabrication and lithography
  • Surface plasmon resononance (SPR) and Total Internal Reflection Fluorescence (TIRF)

Responsibilities will include:

  • Working with Leslie Lab, NMIN and ScopeSys collaborators on background research, literature reviews, and analysis of competing/existing methods/technologies
  • Designing and modifying experimental setups to support research. This may include modifying instruments, consumables, reagents, protocols, analysis methods.
  • Planning and executing detailed experiments. This will entail individual and collaborative work from bench level pipetting through to analysis and reporting.
  • Regularly reporting and documenting plans and results in different formats and timescales, from weekly meetings to grant reports and publications.

Project overview

About CLiC high-throughput single-molecule analysis technology

Our single-molecule imaging technology, Convex Lens-induced Confinement (CLiC), works by squeezing nanoparticles and/or molecules into arrays of nanometer- to micrometer-scale “traps” that are large enough to allow them to move and interact freely, but small enough to keep them confined so they can be imaged over extended periods with a high-powered optical microscope.  By using distinct fluorescent labels for vehicle and cargo, CLiC is capable of simultaneously measuring the size and loading of individual nanoparticle-drug complexes, with high throughput and under cell-like conditions.

Our research program is focused on elucidating the mechanism of complex drug-target interactions, as well as drug uptake and release by nanoparticle delivery vehicles.  The ability to simultaneously observe large numbers of individual nanoparticles offers important advantages over industry-standard “ensemble” measurement technologies like Surface Plasmon Resonance and Dynamic Light Scattering.  These ensemble methods, which are workhorse technologies in the drug development industry, provide a single value that represents an “average” across the large number of molecules being measured. 

Our technology has generated significant excitement in a diverse range of fields, from fundamental biophysical research (effect of DNA super-coiling on drug binding to target sites) to materials science (shape-based catalysis), to drug development (ASO binding to target mRNA) and delivery (nanoparticle vehicles).  Our research helps accelerate the development of complex macromolecular therapies based on antibodies, oligonucleotides, and nanoparticles. 

Other considerations

The Leslie laboratory is situated at the UBC Vancouver campus in the Michael Smith Laboratories.  Aspects of this project may be performed in part as a collaboration with an industry partner.  Experience and co-op internships in industry will be considered strong assets, especially with a fast-paced start-up work on applied research. 

This position is available from May 1st, 2021 and will be based on a one-year renewable contract, extendable depending on funding availability.  The successful candidate will be supported by an NMIN Strategic Initiative grant.

A letter of application, accompanied by a detailed curriculum vitae including a list of publications, and contact details for 3 references, should be sent by email to:

Professor Sabrina Leslie
contact.leslielab@gmail.ca

Please include “PDF search” in the e-mail subject line.  Applications will remain open until the position is filled.  Review of applications will begin immediately and continue until the position is filled.  We will contact you only if invited for an interview.

Equity and diversity are essential to academic excellence. An open and diverse community fosters the inclusion of voices that have been underrepresented or discouraged. We encourage applications from members of groups that have been marginalized on any grounds enumerated under the B.C. Human Rights Code, including sex, sexual orientation, gender identity or expression, racialization, disability, political belief, religion, marital or family status, age, and/or status as a First Nation, Metis, Inuit, or Indigenous person.

 All qualified candidates are encouraged to apply; however Canadians and permanent residents will be given priority.