We are pleased to present two seminars by leading researchers Dr Matthew Baker and Dr Ira Deveson.

Date: Thursday, 28 October

Time: 12 - 1pm

Venue: Online Via Zoom

Click here to access the free seminar.

 

Bionanotechnology in vivo and in vitro: directing evolution of molecular motors and building them from the bottom up

Dr Matthew Baker, University of New South Wales

Matthew Baker works on two systems of nanotechnological interest: 1) the bacterial flagellar motor, the rotary electric nanomachine that powers most bacterial swimming, and 2) using DNA nanotechnology to control and shape lipid membranes. His team's recent work on the flagellar motor concerns the directed evolution of the stators which drive rotation and examining how they are ion selective. We engineered a sodium powered chimeric stator onto the E. coli genome using NO-SCAR CRISPR editing and then evolved it in the lab using iterative swim plating in low sodium environments to pressure the adaptation to sodium-free motility. This gave rise to upmotile variants in only a few days with specific mutations in the pore-lining region. Our work on DNA nanostructures, in collaboration with Shelley Wickham's team at Sydney University, has recently characterised the best conditions to get DNA nanostructures and lipids to work together. Typically, DNA nanostructures use cholesterol moieties to embed in the membrane but a full characterisation of the best way to connect and arrange these cholesterols is lacking. We demonstrated that more cholesterols are not necessarily better, and explored the most suitable linkage chemistry to allow strand displacement, the basis of all reaction and interaction in DNA nanotechnology.

Photo of Rd Matthew BakerAbout Matthew:
Dr Matt Baker is a Scientia Senior Lecturer in the School of Biotechnology and Biomolecular Sciences at the University of New South Wales. Matt completed his DPhil in Physics at Oxford University as a John Monash Scholar studying the bacterial flagellar motor that makes nearly all bacteria swim. Subsequently Matt investigated protein transport in Oxford's Chemistry Research Laboratory and in the Department of Biochemistry. Upon his return to Australia, Matt focussed primarily on how simple subunit interactions govern assembly of complex architectures, including the rotor (NSMB 2016) and filament (eLife 2017). The next question is how this complexity emerged. To begin addressing this, Matt's nascent group at UNSW looks at how ion selectivity changes using directed evolution (Mol Micro 2019, Front. Microbiol. 2020) to examine the evolutionary landscape that constrains the adaptation of the motor (bioRxiv 2021).

 

Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing

Dr Ira Deveson, Garvan Institute of Medical Research 

Short-tandem repeat (STR) expansions are an important class of pathogenic genetic variants. Over forty neurological and neuromuscular diseases are caused by STR expansions, with 37 different genes implicated to date. Here we describe the use of programmable targeted long-read sequencing with Oxford Nanopore's ReadUntil function for parallel genotyping of all known neuropathogenic STRs in a single, simple assay. Our approach enables accurate, haplotype-resolved assembly and DNA methylation profiling of expanded and non-expanded STR sites. In doing so, the assay correctly diagnoses all individuals in a cohort of patients (n = 27) with various neurogenetic diseases, including Huntington's disease, fragile X syndrome, cerebellar ataxia (CANVAS) and others. Targeted long-read sequencing solves large and complex STR expansions that confound established molecular tests and short-read sequencing, and identifies non-canonical STR motif conformations and internal sequence interruptions. Even in our relatively small cohort, we observe a wide diversity of STR alleles of known and unknown pathogenicity, suggesting that long-read sequencing will redefine the genetic landscape of STR expansion disorders. Finally, we show how the flexible inclusion of pharmacogenomics (PGx) genes as secondary ReadUntil targets can identify clinically actionable PGx genotypes to further inform patient care, at no extra cost. Our study addresses the need for improved techniques for genetic diagnosis of STR expansion disorders and illustrates the broad utility of programmable long-read sequencing for clinical genomics.

Photo of Dr Ira DevesonAbout Ira:
Dr Ira Deveson is an early career researcher at the Garvan Institute of Medical Research with expertise in genomics, biotech development & bioinformatics. Ira leads the Genomic Technologies research group within Garvan's Kinghorn Centre for Clinical Genomics. His current focus is on the development and implementation of long-read sequencing technologies in a diverse set of research areas – ranging from clinical genome analysis to reptile sex determination. Ira previously completed a PhD (2014-2017) and post-doc (2018-2019) at the Garvan Institute under Dr Tim Mercer. He is supported by an MRFF Investigator Grant and philanthropic funding from the Kinghorn Foundation.

About AIBN Seminar Series

The AIBN Seminar series showcases a range of seminars across different topics and disciplines

Venue

Online via Zoom