16.12.2022
— drug discovery, electrophysiology, ion channels, iPSC, Sophion, stem cells
Developing iPSC ion channel recordings with automated patch clamp
Induced pluripotent stem cell (iPSC) techniques have been developing over the last few years, improving cell differentiation and maturation. In combination with improved culturing and handling, iPSC ion channel recordings via automated patch clamp (APC) have made these model ‘adult’ differentiated cells extremely useful in biomedical research, more translatable in defining human physiology and disease, whilst reducing the need and use of animal tissue.
Over 2022, Sophion scientists, collaborators, and users of our platforms have been at the forefront of this iPSC and APC revolution. Our collaborative research is captured here:
Webinars
Mike Hendrickson (BrainXell) & Daniel Sauter on iPSC-motor neurons:
Liz Buttermore (Human Neuron Core, Boston Children’s Hospital) & Kadla Rosholm on iPSC-cortical neurons:
Will Seibertz (University Medical Center Göttingen) & Kadla Rosholm on iPSC-cardiomyocytes:
Review paper
Adventures and Advances in Time Travel With Induced Pluripotent Stem Cells and Automated Patch Clamp. Rosholm et al., Frontiers Mol. Neurosci., 2022: view
Are you interested in learning more about the research performed on Sophion automated patch clamp platforms and stem cells? We have gathered a list of relevant publications here
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30.03.2022
— automated patch clamp, drug discovery, Large Molecules, QPatch, QPatch II, Qube 384, Sophion
Large molecule characterization using automated patch clamp
Automated patch clamp solutions have been used for years to routinely research ion channels on large molecules. Being able to screen and characterizing large molecules on automated patch clamp is the key to ensure an efficient drug discovery process.
Today, more than 90% of all approved drugs are coming from research on small molecules, but large molecules research is rapidly rising in prominence. The importance of drug discovery already constitute the lion’s share of the top 10 selling drugs worldwide.
Large molecules have gained more attention due to their mode of action, often achieving greater target specificity and potency than small molecule drugs.
Learn more about the various classes of large molecules and ion channel research on our Qube and QPatch solutions here
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06.12.2021
Sophion at the forefront of cardiac ion channel electrophysiology
Cardiac ion channels are critical in the generation and maintenance of the cardiac action potential which drives the heartbeat. Consequently, cardiac ion channel safety assessment of new chemical entities (NCEs) for any new drug approval is a critical element of drug discovery.
In two recent publications, Sophion scientists have added to the cardiac ion channel field.
In collaboration with Toho University, Kazuya Tsurudome, Hironori Ohshiro and Taku Izumi, scientists from Sophion’s Tokyo labs, generated Qube data on the anti-atrial fibrillatory drug Oseltamivir against a panel of cardiac ion channels.
The second publication co-written by Damian Bell and Bernard Fermini, the highly experienced cardiac safety pharmacologist, was a review on automated patch clamp, the latest developments in functionality, how APC has been adopted and is changing cardiac safety assessment in drug discovery.
Read more about cardiac ion channels and Qube/QPatch here.
Oseltamivir effects on 5 cardiac ion channel currents – figure copied from Kambayashi et al., Frontiers in Pharmacology, 2021Contact
13.10.2021
Tricky CRAC channels not so tricky on Qube and QPatch
Calcium release-activated calcium (CRAC) ion channel currents (ICRAC) are critical in many diseases. Compounds modulating ICRAC have been developed towards treatment for autoimmunity (e.g. rheumatoid arthritis, multiple sclerosis, diabetes, inflammatory bowel disease, psoriasis, mast cell-related disorders), metastatic breast cancer, cardiovascular and cerebrovascular diseases and viral infections, and may help to prevent transplant rejection.
One of the most advanced CRAC drug discovery programmes has been performed by CalciMedica, with their Auxora compound in clinical trials for diseases as diverse as pancreatitis & Covid-19.
The ability to efficiently record these channels on automated patch clamp (APC) would be advantageous. However, some APC platforms struggle to make recordings without ‘seal enhancer’ solutions containing high calcium and fluoride, both ions cause problems recording ICRAC.
Addressing this tricky channel on APC, Sophion’s scientists have successfully recorded ICRAC on QPatch and Qube without the need for problematic calcium or fluoride.
For more info & publications on CRAC channels and efficient APC recordings, click here.
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06.10.2021
TRP channels, Nobel prizes and Automated Patch Clamp
The breakthrough discoveries in this year’s Nobel Prize laureates for physiology or medicine enable us to understand how heat, cold and mechanical forces can initiate the nerve impulses that allow us to perceive and adapt to the world around us. Read more about this year’s laureates here.
At Sophion, we are excited that the prize again this year goes to laureates working in the field of ion channels.
TRP channels are critical for our ability to perceive temperature and also play important roles in nociception, including neuropathic & inflammatory pain pathways. The Piezo channels endow us with the sense of touch and the ability to feel the position and movement of our body parts (proprioception).
Of course, we have worked on these ion channels for years. While our research at Sophion does not qualify for a Nobel prize (at least not yet), nonetheless, we are proud that our systems contribute to the further understanding of the functionality of these vital membrane proteins.
In honour of this year’s laureates and for those of you that would like to learn more about TRP channels, we have gathered some TRP-themed videos from previous Sophion ICMS symposia for you to watch over morning coffee. If you want to learn even more, check out the list of peer-reviewed publications, application reports and posters below.
As always, if interested in setting up new assays on your QPatch II or Qube 384 or optimizing your existing assay, we recommend discussing this with your dedicated (soon to be laureated?) Application Scientist.
Publications
Barilli A, Aldegheri L, Bianchi F, Brault L, Brodbeck D, Castelletti L, et al. From High-Throughput Screening to Target Validation: Benzo[d]isothiazoles as Potent and Selective Agonists of Human Transient Receptor Potential Cation Channel Subfamily M Member 5 Possessing In Vivo Gastrointestinal Prokinetic Activity in Rodents. J Med Chem [Internet]. 2021 May 13 [cited 2021 Jul 6];64(9):5931–55. LINK
Sunesen M, Jacobsen RB. Study of TRP Channels by Automated Patch Clamp Systems. In: Islam MS, editor. Transient Receptor Potential Channels [Internet]. Dordrecht: Springer Netherlands; 2011. p. 107–23.
Application reports and posters
Jensen 2008. TRPM8 tested on QPatch. Sophion Application Report.
Whilst we far prefer to see and support our users in person, sometimes for both you and us it’s easier, more efficient & practical to point you in the direction of our excellent video tutorials. These tutorials cover many aspects of the most common aspects of maintenance and data analysis.
Unlike our application scientists and field service engineers that need to rest – they’re good, pretty close to super-human, but even they need to sleep occasionally – these handy tutorials will always be at your side 24/7/365.
So, whether you need to clean your bed-of-nails, save a debug file for us to do a deeper dive into your APC’s performance and data or brush up on your data analyses like grouped Hill fits in Sophion Analyzer, we’ve got you covered.
See more video tutorials here, where you can also see our services for additional courses and training:
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07.09.2021
— drug discovery, ion channels, Ion channels and cancer
Ion Channels and Cancer
Ion channels are critical signaling proteins in all of the main hallmarks of cancer – see image above. Indeed, Prof. Saverio Gentile of the University of Illinois, Chicago, has pithily defined this inextricable connection as ‘a channelopathy called cancer’.
Sophion are at the forefront of ion channel research supporting and collaborating with world-leading oncochannelopathy labs, including hosting presentations on their findings at our Ion Channel Modulation Symposia, User Meetings & webinars.
Links to recordings of these lectures are given below.
Optogenetics uses light to activate (depolarize) or inhibit (hyperpolarize) cells genetically engineered to express light-gated ion channels. In this way, control of a cell’s membrane potential can be controlled by light, allowing fast & precise control only in the cells expressing the light-gated ion channels. Channelrhodopsins (e.g. ChR2) are cation channels that when gated by light will depolarize the cell membrane; halorhodopsin (e.g. NpHR) is a chloride ion pump that can be used to hyperpolarize the cell membrane.
Short ligand exposure time A) RuBi-GABA activation followed by wash-out B) RuBi-GABA activation during perfusion Compound consumption: 7 µL/site. For more info see application report by Boddum 2019
By combining these optogenetic actuators with cell-type specific gene promotors & using viral delivery (e.g. adenovirus), very specific neurons within a neural circuit can be targeted in vivo to define roles & mechanisms in behaviours in live, active animals.
Unsurprisingly this very powerful technique has many applications & would not be hyperbole to say it’s revolutionized neuroscience. Indeed, Nature made it their method of the year for 2010. Barring the Nobel Prize, which is sure to follow, all the main scientific prizes & plaudits have been awarded to Georg Nagel, Peter Hegemann, Ernst Bamberg & Karl Deisseroth, the scientists who invented & developed this technique.
The ability to control membrane voltage by both voltage-clamp & optogenetics on an automated patch clamp platform with the flexibility & potential this may afford researchers was not lost on Sophion. By 2018 we had developed a functional Qube with LED arrays to perform simultaneous voltage-clamp & optogenetic light control of membrane voltage. Using ‘Qube Opto’ we have now produced a book chapter, application reports & presentations.
For more info on how Qube Opto might be used in your research see the links below or contact us at info@sophion.com.
Optical modulation of ion channels using Qube Opto (Poster). Kim Boddum, Peder Skafte-Pedersen, Jens Henneke, Daniel Sauter, Jean Francois Rolland, Jiaye Zhang, Sandra Wilson 2019. Sophion Bioscience, Cranfield University, Axxam S.p.A.
Ion channel modulation through secondary messenger. Through activation of the photoactivatable adenylyl cyclase, bPAC with 500 ms long light pulses at λ = 475 nm with a frequency of 0.5 Hz, it was possible to increase intracellular levels of cAMP and thereby modifying the co-expressed HCN2 channel. For more info see poster by Schupp et Al 2018
If you are interested in developing new assays, set up collaborations on optogenetics/optopharmacology or have ideas for future work lets talk.
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15.07.2021
Q2 sees a bumper crop of 15 publications using Qube 384 and QPatch
Q2’s bumper crop of papers is a nice mix of industry & academic institutions – see the list of contributing labs below. The 15 publications cover a broad range of ion channels (P2X7, hERG, NMDAR, nicotinic acetyl choline receptors, TRPM5, Kv7.2/7.3) & research (Alzheimer’s, multiple sclerosis, cancer, schizophrenia, amnesia, chronic pain, diabetes, anti-bacterials, epilepsy).
Two of the publications were Sophion authored on cardiac ion channel pharmacology. In collaboration with Toho University, Tokyo, Kazuya Tsurudome, Hironori Ohshiro & Taku Izumi studied the anti-atrial fibrillation drug Oseltamivir. A second publication written by Damian Bell & Bernard Fermini – one of the godfathers of cardiac safety pharmacology – is a wide-ranging review on APC in safety assessment.
Finally, what quarter would be complete without yet more great research emanating from the publishing machine that is the University of Queensland.
In Jiang et al., Glenn King’s lab have published on a tarantula toxin that blocks Nav1.7 ion channels, showing its ability to reduce chronic visceral pain in irritable bowel syndrome (IBS).
Jensen et al., another paper involving the King lab in collaboration with Jennifer Deuis, Irina Vetter & Samuel Robinson’s labs, have done a deep dive into the venomous peptides of the velvet ant.
The velvet ant (Dasymutilla klugii) – from Jensen et al., U. Queensland
Here you can see all the latest publications:
Kambayashi et al., 2021 Translational Studies on Anti-Atrial Fibrillatory Action of Oseltamivir by its in vivo and in vitro Electropharmacological Analyses
Jensen et al, 2021 Venom chemistry underlying the painful stings of velvet ants (Hymenoptera: Mutillidae)
Hopper et al., 2021 Synthesis and Characterization of the Novel Rodent-Active and CNS-Penetrant P2X7 Receptor Antagonist Lu AF27139
Bell, D.C. & Fermini, B., 2021 Use of automated patch clamp in cardiac safety assessment: past, present and future perspectives
Li et al., 2021 Identification of poly(ADP-ribose)polymerase 1 and 2 (PARP1/2) as targets of andrographolide using an integrated chemical biology approach
Schuelert et al., 2021 The Glycine Transport Inhibitor Bi 425809 Restores Translatable EEG Deficits in an Acute Mouse Model for Schizophrenia-Related Sensory Processing and Cortical Network Dysfunction
Paradkar et al., 2021 Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore
Ledneczki et al., 2021 HTS-based discovery and optimization of novel positive allosteric modulators of the α7 nicotinic acetylcholine receptor
Díaz et al., 2021 Tricyclic Triazoles as σ1Receptor Antagonists for Treating Pain
Barilli et al., 2021 From High-Throughput Screening to Target Validation: Benzo[d]isothiazoles as Potent and Selective Agonists of Human Transient Receptor Potential Cation Channel Subfamily M Member 5 Possessing In Vivo Gastrointestinal Prokinetic Activity in Rodents
Lapointe et al., 2021 Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria.
Ottosson et al., 2021 Synthetic resin acid derivatives selectively open the hKV7.2/7.3 channel and prevent epileptic seizures.
Kong et al., 2021 Design, Synthesis, and Biological Evaluation of Novel Pyrimido[4,5-b]indole Derivatives Against Gram-Negative Multidrug-Resistant Pathogens
Jiang et al., 2021 Pharmacological Inhibition of the Voltage-Gated Sodium Channel NaV1.7 Alleviates Chronic Visceral Pain in a Rodent Model of Irritable Bowel Syndrome
Zheng et al., 2021 Discovery of Methylene Thioacetal-Incorporated α-RgIA Analogues as Potent and Stable Antagonists of the Human α9α10 Nicotinic Acetylcholine Receptor for the Treatment of Neuropathic Pain
