Student stories

Novel small molecule modulation ofPIEZO1 channels

Tools:
SyncroPatch 384

Dr. Jacob Kinsellafeatured by Nanion Technologies
Jacob Kinsella completed his PhD at theCan you give us a brief summary of your PhD?

University of Leeds, UK, studying mechanicalactivation of PIEZO1. During his PhD, Jacob“The aim of my PhD project was to identify novel structurally

spent two months at Nanion working with theunique inhibitors of the PIEZO1 mechanosensitive ion

SyncroPatch 384. Jacob recently completedchannel.”his PhD and is currently taking some time out
to travel and invest in his pastimes such as

What brought you to Nanion?

hiking, climbing and camping.

“Professor David Beech has had a longstanding and highly
successful collaboration with Nanion who has long shown agreat interest in PIEZO1. The successful mechanical activation
Introduction
There are a number of ion channels which are mechanically
activated and play a vital role in sensing mechanical forces
in various cell types. One type of mechano-activatedion channel is PIEZO1, a cation channel activated bymechanical force. Dysfunction of PIEZO1 has been
associated with numerous pathophysiological states,
including generalized lymphatic dysplasia, varicose veindisease, and hereditary xerocytosis. Therefore, PIEZO1 is apotential therapeutic target and finding ways to study suchmechanosensitive channels using high throughput techniquesis critical for drug discovery.
Jacob has a background in medicinal chemistry, completing
his first degree at the University of Manchester, following
which he undertook his PhD at the University of Leeds under
the supervision of Prof. David Beech investigating analoguesof Yoda1 to activate PIEZO1. As part of Nanion’s continued
commitment to academic research and supporting young
researchers, Jacob was invited to spend some time at Nanion
to optimize the PIEZO1 assay and supplement his PhD thesis.

Jacob enjoying some time with Nanion colleagues
on the terrace. During Jacob’s time at Nanion’s
headquarters, he enjoyed socializing with friends
and colleagues on Nanion’s roof terrace, pictured
here with Markus and Tom.

of the PIEZO1 channel with the SyncroPatch 384 marked afantastic milestone in the automated patch-clamp field andinspired the idea that a slightly modified protocol may be
used to screen a small library of compounds. After a brief
discussion, Nanion kindly offered to host me in their Munich
office to develop the proposed assay and flesh out mythesis.”
What was your project at Nanion?
“My project was to further optimize the automatedmechano-patch-clamp assay developed by Nanion with afocus on increasing its response rate to a level sufficient for
testing a medium-sized library of small molecules.”“My colleagues at Nanion were some of the most welcoming andfriendliest people I’ve ever had the pleasure to work with.”
Dr. Jacob Kinsella, University of Leeds

Was your project work at Nanion related to your PhD?

Which instruments did you use at Nanion?

“I was very fortunate that the project at Nanion was“My work was conducted entirely on the newest iteration of

directly related to my PhD project. The work conducted at

the SyncroPatch 384 which was an absolute pleasure to work

Nanion contributed significantly to my project’s strategic

with. We were able to take advantage of the adjustabledevelopment and greatly influenced the overall qualitypipette speed of the SyncroPatch 384 and position theof the thesis than I initially imagined it would. I was able

pipette very close to the cell which meant that we could

to publish the work in the British Journal of Pharmacology

obtain high mechanical forces at the cell and reproducibly(Improved PIEZO1 agonism through 4-benzoic acidactivate PIEZO1. What is more, we could repetitively pipettemodification of Yoda1) and travel to San Diego and present

up and down close to the cell and saw effects on the PIEZO1a poster at the Biophysical Society Annual Meeting which I

response. This procedure became known unofficially as ‘cell

thoroughly enjoyed.”massage’ at Nanion.”
Did your project at Nanion accelerate your PhD project?
“Absolutely! The SyncroPatch 384 afforded me the ability
to test 60 inhibitors against the PIEZO1 channel. While thisis possible with the conventional manual patch-clamp
technique, using the SyncroPatch 384 was significantly
less time-consuming saving me months of work. The data
generated from the SyncroPatch 384 allowed me to selectpromising compounds before testing them in orthogonal
assays.”What was your best moment during your time at Nanion?
“Aside from frequently raiding the stocks of apfelschorle,
Haribo and Kinder, I would say that it was creating lasting
friendships. My colleagues at Nanion were some of the mostwelcoming and friendliest people I’ve ever had the pleasure
to work with. An honorable mention to the very regularparties. It was through these that I developed my newfoundlove for Munich beers, particularly Augustiner.”

Investigating small molecule modulators of PIEZO1. Jacob
presented his work at the Biophysical Society AnnualMeeting in 2023 in San Diego in a poster presentation andco-authored a paper in the British Journal of Pharmacology
in 2022.

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