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.
アプリケーションレポートおよびポスター
Jensen 2008. TRPM8 tested on QPatch. Sophion Application Report.
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.
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
出版論文一覧:
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
