Editor’s Collection: Meet the authors – Nathalie Busschaert et al.

Meet our researchers:

Elliot Williams

Hassan Gneid

Sarah Marshall

Mario González

Jorgi Mandelbaum

Nathalie Busschaert

Elliot Williams
obtained his BSc in biochemistry from the University of Central Florida. He is currently working towards his PhD at Tulane University. His PhD focuses on the development of hosts for bacterial lipids, in particular anionic lipids such as PG. As such, he was the first author of the paper and performed the majority of the experiments. When not in the lab, he likes to dance, engage in his community, and walk his dog.

Hassan Gneid completed a BSc in chemistry at Damascus University (Syria), in the field of applied chemistry. After a number of years working in industry, he returned to education in 2011 to complete an MPhil degree in chemistry at the University of Southampton (UK) under the supervision of Dr. Martin Grossel. In 2014, he joined the group of Dr. Jonathan Watts to pursue a PhD in chemistry at the University of Southampton (UK) and the RNA Therapeutics Institute (USA). His PhD work revolved around the use of antisense oligonucleotides for the development of novel antibiotics. Hassan joined the Busschaert group in 2020 as a post-doctoral researcher responsible for microbiology studies. His research interests are oligonucleotide therapeutics and antibiotic development.

Sarah Marshall received her B.S. in biology from the Honors College at East Carolina University in 2015. She continued at East Carolina University to receive her M.S. in chemistry under the supervision of Dr. William E. Allen. During her M.S., she focused on the development of fluorescent amino acids and peptide synthesis. Currently, Sarah is a PhD candidate in the Busschaert group at Tulane University, working on various medical and non-medical applications of synthetic transmembrane anion transporters.

Mario González was born in San Juan, Puerto Rico. In 2019, he received his B.S. in Chemistry from the University of Miami. That same year, he joined the Busschaert group at Tulane University as a graduate student working towards a PhD. His current research involves turning commercially available, nonselective sensors selective via liquid-liquid extractions.

Jorgi Mandelbaum graduated from Tulane University with a B.S. (2021) and M.S. (2022) in neuroscience, with undergraduate minors in chemistry and Spanish. During her studies, she performed undergraduate research in the lab of Dr. Nathalie Busschaert, focusing on PG binding. She currently works as Research Scientist II on the Translational Pharmacology team in the Ophthalmology department at Novartis Institutes for BioMedical Research in Cambridge, MA. With her passion for pharmaceutical development, Jorgi is excited to be continuing her research beyond the academic setting in the healthcare industry.

Nathalie Busschaert born in Antwerp, Belgium, completed a BSc in chemistry at the K. U. Leuven, Belgium, and continued studying for an MSc in chemistry at the same university. She then moved to the University to Southampton (UK) in 2010 to undertake a PhD under the supervision of Professor Philip A. Gale, working on the development of synthetic transmembrane anion transporters. In 2015 she joined the group of Andrew Hamilton at the University of Oxford to work as a post-doctoral researcher. In January 2016 she followed prof. Andrew Hamilton to New York University. She is currently working as an assistant professor at Tulane University. Her research interests are ion transport, lipid binding, membrane processes and medicinal applications of supramolecular systems.

What inspired your research in this area?

We are a young research group (established July 2017), and have been looking for a way to carve out our reputation as supramolecular chemists that work towards medical applications. I have been intrigued by the activity of antimicrobial peptides for a long time, due to my interest in biological membranes. Antimicrobial peptides have long been hailed as a solution to the antibiotic resistance crisis, because they target the bacterial membrane and can cause quick bactericidal activity in bacterial cells. However, they have some drawbacks and have not been able to completely live up to their expectation yet. Most antimicrobial peptides are cationic amphiphilic compounds that function by binding to the negatively charged lipids of bacterial membranes, followed by membrane disruption. During my own PhD that focused on the development of small neutral molecules that can transport chloride anions across biological membranes, we often observed binding to the lipid headgroup in molecular dynamics modelling. While binding to the lipid headgroup is detrimental for anion transport, I hypothesized that binding to the headgroup can provide membrane selectivity (e.g., bacterial membranes over human membranes) and can induce membrane perturbations similar to those observed for antimicrobial peptides. From the start of my independent career, my research group therefore started to develop small molecules that can strongly and selectively bind to bacterial lipid headgroups.

What do you personally feel is the most interesting/important outcome of your study?

The most important outcome of our study is that we provided proof-of-principle that small, neutral, structurally simple molecules can selectively bind to lipid headgroups and that this binding event has sufficient impact on membrane permeability to induce antibacterial activity. Even though the reported compounds were our first attempt at binding PG lipids and have not underwent further optimization yet, we have already achieved relatively potent antibiotics with minimum inhibitory concentrations (MIC values) of 12.5 – 25 μM.

What directions are you planning to take with your research in future? What are you going to be working on next?

We are preparing analogs of the PG hosts reported in this paper (https://doi.org/10.1039/D1OB02298A ), as well as the PE hosts that were reported in our previous OBC paper (https://doi.org/10.1039/D1OB00263E). The aim is to improve the antibacterial activity and lipid selectivity, and to elucidate structure-activity relationships that can help other researchers develop hosts for these two important bacterial lipids. In addition, we would like to investigate the effect of physical membrane parameters (such as curvature, and lipid chain length) on the binding of the hosts to the lipid headgroup. Finally, we are working on developing hosts that can bind selectively to other types of biologically relevant lipids.

Read the full article: A supramolecular host for phosphatidylglycerol (PG) lipids with antibacterial activity

See the other articles showcased in this month’s Editor’s Collection

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