Dr. Douglas Kell, University of Liverpool Research Chair in Systems Biology, investigates the transport of fluorescent small molecules across the plasma membrane. His work necessitates the often difficult rapid screening of up to 50 fluorophores at the same time. He discovered the solution through advanced flow cytometry.
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Drug transport through the membrane
The plasma membrane is what isolates the cell’s interior from its surroundings. It is made up of a lipid bilayer and other macromolecules, such as carbohydrates, glycoproteins, and membrane proteins, which provide structure and restrict molecule transport across the cell.
The physical and chemical properties of a drug molecule determine its route into the cell. Most lipid-soluble drugs, for instance, can cross the membrane passively via the diffusion process. Other drugs enter the cell passively or actively by imitating the natural substrates of transporter proteins.
Scientists can reliably predict potential drug interactions, treatment efficacy, and resistance mechanisms if they know which transporter(s) a drug uses.
Dr Douglas Kell’s work on small molecule transport
Dr Kell’s lab is interested in small molecule transport across cellular membranes. His research is based on mammalian cell membrane transporters and bacterial transporters, several of which have yet to be identified. His group employs advanced flow cytometry to identify the uptake of small fluorescent molecules, which have previously had high structural similarity to several small molecule pharmaceuticals.
Recent research identified the molecular transporters responsible for psychoactive drug uptake into mammalian cells. They established competitive assays between the drugs of interest and their fluorophore mimics to answer this question. They utilized advanced flow cytometry to evaluate cell transport into mammalian cells by knocking out specific transporter proteins.
Why high throughput flow cytometry
The Kell lab uses the iQue® Advanced Flow Cytometry Platform for their research for several reasons:
- Rapid analysis: The equipment is one of the fastest flow cytometers, helping them get more done in a day
- High throughput: The iQue® can tackle 96 and 384 well plates, enabling the screening of numerous fluorescent small molecules at once
- Versatility: It can identify small cells, so they can investigate the membrane biology of both mammalian cells and E.coli
- Performance: The system provides sophisticated data, making it easy to identify intracellular fluorescence signals without interference from extracellular noise
Other projects in the lab include screening up to 50 fluorophores for transport into E. coli cells and using fluorophores to identify microbial cell proliferation after antibiotic treatment, with the goal of developing a rapid anti-microbial susceptibility test for urinary tract infections.
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