Our next webinar will take place via the internet on Tuesday June 15th at 11AM EDT/4PM GMT. Sign up on our mailing list to receive the Zoom link!
We hope to see/hear from you all at one of our sessions or as one of the next speakers. If you are an early career scientist and would like to present your research, don't hesitate to submit an abstract today! For now, please learn more about our current speakers and their research below. We also thank the generous support from Cell Reports Physical Science.
Our featured speakers this week are Lydia Stariha (graduate student, Duke University, USA), Dr. Nicola Bell (postdoc, University of Glasgow, UK), and Dr. Eden Tanner (assistant professor, University of Mississippi, USA). The seminar will be guest-moderated by Dr. Micaela Matta from the University of Liverpool.
LEARN MORE ABOUT THE SPEAKERS AND THEIR TALKS BELOW
LYDIA STARIHA (on twitter @lydiastariha)
Biography: Lydia Stariha is a fourth year PhD candidate in the Chemistry Department at Duke University. Originally from La Salle, Illinois, Lydia graduated from Grinnell College in 2017 earning a degree in Biochemistry. For her graduate studies, she joined the lab of Dr. Dewey McCafferty. Her research employs chemical biology tools to investigate structural and biosynthetic elements of lipid II-binding antimicrobials to enhance our understanding of this important class of antibiotics.
Title of Talk: Discovery of the Class I Antimicrobial Lasso Peptide Arcumycin
Abstract: Lasso peptides are a structurally diverse superfamily of conformationally-constrained peptide natural products, of which a subset exhibits broad antimicrobial activity. Although advances in bioinformatics have increased our knowledge of strains harboring the biosynthetic machinery for lasso peptide production, relating peptide sequence to bioactivity remains a continuous challenge with fewer than half of the members of this family isolated to date having been tested for biological activity. Towards this end, a structure-driven genome mining investigation of Actinobacteria-produced antimicrobial lasso peptides was performed to correlate predicted primary structure with antibiotic activity. Through this work a distinct relationship between phylogenetic lineage and structural class, as determined by the number and location of disulfide bonds, was observed. Further bioinformatic evaluation revealed eight putative novel class I lasso peptide sequences. This subset is predicted to possess antibiotic activity as characterized members of this class have both broad spectrum and potent activity against Gram-positive strains. Fermentation of one of these hits, Streptomyces NRRL F-5639, resulted in the production of a novel class I lasso peptide, arcumycin, named for the Latin word for bow or arch, arcum. The structure of arcumycin was elucidated using a mass spectrometry approach to confirm both sequence and topology. Arcumycin exhibited antibiotic activity against Gram-positive bacteria including Bacillus subtilis (4 µg/mL), Staphylococcus aureus (8 µg/mL), and Micrococcus luteus (8 µg/mL). Arcumycin treatment of B. subtilis liaI-β-gal promoter fusion reporter strain resulted in upregulation of the system liaRS by the promoter liaI, indicating arcumycin interferes with lipid II biosynthesis. This preliminary result of cell wall inhibition presents a conserved mechanism of action among Actinobacteria-produced lasso peptides that had not previously been elucidated. Cumulatively, this work illustrates the relationship between phylogenetically related lasso peptides and their bioactivity as validated through the isolation, structural determination, and evaluation of bioactivity of the novel class I antimicrobial lasso peptide arcumycin.
DR NICOLA BELL (on twitter @NickelCarbon)
Biography: Dr Nicola Bell is a Senior Research Fellow in Automated Inorganic Chemistry at the University of Glasgow and the Group Coordinator of The Cronin Group. Nicola obtained her PhD at the University of Edinburgh and went on to a Postdoctoral Fellowship with Prof. Polly Arnold on Actinide chemistry. Before moving to Glasgow Nicola briefly dipped her toe in the world of organic chemistry, developing the Ionising Cross coupling methodology at the University of St Andrews. Outside of the lab Nicola is a passionate advocate for the use of science & evidence in policy making as well as being an avid film fan.
Title of Talk: Ionising Cross Coupling
Abstract: Transition metal‐mediated cross‐coupling is an essential synthetic method, used extensively throughout the chemical industry for the synthesis of pharmaceuticals, agrochemicals, natural products, and materials. C–N cross‐couplings, such as the oxidative Chan-Lam coupling, generally form C−N bonds by reductive elimination from metal complexes bearing covalent C‐ and N‐ligands yielding relatively unreactive, charge-neutral products. This talk will present a novel Cu‐mediated C–N cross‐coupling that uses a dative N‐ligand in the bond‐forming event, which, in contrast to conventional methods, generates reactive cationic products. Mechanistic studies suggest the process operates via transmetalation of an aryl organoboron to a CuII complex bearing neutral N‐ligands, such as nitriles or N‐heterocycles. Subsequent generation of a putative CuIII complex enables the oxidative C–N coupling to take place, delivering nitrilium intermediates and pyridinium products. The reaction is general for a range of N(sp) and N(sp2) precursors and can be applied to drug synthesis and late‐stage N‐arylation, and the limitations in the methodology are mechanistically evidenced.
DR EDEN TANNER (on twitter @EdenTanner)
Biography: Dr. Eden Tanner completed her undergraduate degree with Honors in Advanced Science as a Chemistry major at the University of New South Wales, Sydney, Australia. She earned her doctorate in Physical and Theoretical Chemistry at the University of Oxford and completed her Postdoctoral Research Fellowship at Harvard University working with Samir Mitragotri. As of August 2020, Dr. Tanner is an Assistant Professor in the Department of Chemistry and Biochemistry at the University of Mississippi. The Tanner Lab works at the interface of Chemistry and Bioengineering to solve outstanding biomedical challenges, with a particular focus on the use of ionic liquids in nanoparticle drug delivery.
Title of Talk: Ionic Liquids as Antifouling Polymeric Nanoparticle Coatings
Abstract: One of the major challenges facing intravenous nanoparticle administration is the formation of protein coronae on the surface of injected nanoparticles, which prevents them from reaching the target tissue. Biocompatible ionic liquids (ILs) have been shown to have tunable interactions with biomolecules including proteins and are prone to rearrangement on charged surfaces. We show that this can be exploited to use designer protein avoidant-ionic liquids as polymeric coatings, which can protect the nanoparticle from being fouled by serum proteins in the blood. When the IL coated poly(lactic-co-glycolic acid) (PLGA) particles are injected into mice, they show reduced clearance compared to control poly(ethylene glycol) or bare PLGA particles. Instead of lung, kidney or splenic deposition, the IL-particles accumulate in the lung tissue after hitching a ride on red blood cells post-injection. This talk will discuss the development of ionic liquids for efficacious nanoparticle drug delivery, elucidate the lessons learnt thus far, describe the many challenges to come, and highlight the opportunities that arise at the intersection of physical chemistry and bioengineering.