Jette, Author at Sophion
Safety pharmacology with aging population Sophion paper

Sophion authored paper addresses the challenge of safety pharmacology in the elderly

Despite the looming problems that a growing elderly population causes drug discovery, limited, concrete solutions have been offered to address medicinal developments for the elderly. This threatens to engulf societies across the world.

In a thought-provoking review, ex-Pfizer safety pharmacology expert Bernard Fermini and Sophion scientist Damian Bell have called on the drug discovery community to open discussions and act to develop and implement adequate, robust, and safe testing of medicines for the aging demographic.

We have made the review open access (no paywall), read the paper in full here

Sophion-hiPSC-derived-cell-lines

Latest advances in stem cell recordings on APC reviewed

A Sophion authored pluripotent stem cells and APC review paper shows the much-vaunted use of hiPSC in biomedical research is drawing closer to the promise they hold for safety pharmacology, drug discovery, and personalized medicine.

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Research scientist Kadla Røskva Rosholm, Ph.D., and colleagues at Sophion Bioscience, in conjunction with co-authors Prof. Niels Voigt and scientist Fitzwilliam Seibertz of the University of Göttingen have written a wide-ranging review of techniques and applications of hiPSC, developments driven by high-throughput APC.

Sophion-hiPSC-CM-current-clamp

This figure illustrates paced action potentials in 10 individual hiPSC-cardiomyocyte current clamp recordings from a single measurement QPlate. The expanded action potential shows typical AP characterization measurements: threshold potential (Vt), peak potential (Vp), hyperpolarization potential (Vh), and action potential duration at 90% repolarization (APD90).

View the full, open access paper here

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Successful hERG recordings at 22°C and 35°C on QPatch II

When conducting your ion channel experiments a key environmental factor to consider is temperature. In this latest application report, the conductance, kinetics and pharmacology of the hERG ion channel current, a critical component of the cardiac action potential, were recorded at 22°C and 35°C.

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Like nearly all physiological processes, the activity and pharmacology of ion channels are highly dependent on temperature. Whether making ion channel recordings at mammalian body temperature (~35°C) or simply a consistent room temperature (RT), it is imperative to accurately control the temperature of your recordings. Even ‘simply’ ensuring all your recordings are not subject to the particular vagaries of the lab’s diurnal/seasonal micro-climate can be challenging. With temperature control, by setting the recording site to RT means accurately recording and reporting at 22°C, not the 18-27°C that we all know can be the real world lab RT.

If you want to learn more about temperature control on Sophion’s platforms, read more here

 

Sophion-Webinar-APC-and-hiPSC

Did you miss our second webinar on APC and iPSC from last week?

Research in iPSC holds huge promise for drug discovery. With Sophion’s automated patch technology, we can begin to understand the functional changes taking place in neurons with loss of CDKL5 function.

Last week, guest speaker Elizabeth Buttermore, from Boston Children’s Hospital and Kadla Røskva Rosholm, from Sophion Bioscience presented in collaboration their latest research on cellular, molecular and electrophysiological characterization of CDKL5 deficiency disorder iPSC-derived neurons.

From all over the world, we were happy to see so many engaged and interested participants.

You can see the recorded webinar below:

Sophion-alpha-cobratoxin

Collaborative paper on antibodies neutralizing cobratoxin published by the University of Toronto, Technical University of Denmark and Sophion Bioscience

Snakebite affects some of the poorest populations across the globe and was designated a neglected tropical disease (World Health Organisation, 2017).

In further seminal developments, Sophion has helped to develop and characterize the next generation of monoclonal antibodies to neutralize a key alpha-cobratoxin in the venom of the monocled cobra. The antibodies were discovered and developed via phage display by collaborators at the University of Toronto and the Technical University of Denmark. Their in vitro functional, neutralizing effect on the nicotinic acetyl choline receptor (nAChR) ion channel was determined on QPatch II.

Find the paper published in Protein Science here

Collaborative paper on antibodies neutralizing cobratoxin

Assessment of the in vitro neutralization potency of the top two IgGs was performed via electrophysiological measurements using whole cell patch-clamp. The blockade of ACh-dependent currents by purified α-CTx was reversed by pre-incubation of the toxin with serial dilutions of blocking IgG. Signals were normalized to full response (in the absence of α-CTx and IgG).

Large Molecules: New application report focus on Wnt signaling pathway activation

In a new application report, written together with Dr. Aamir Ahmed from Kings College London, UK, we obtained automated patch clamp (APC) recordings using the fragile and scarce Wnt proteins. Wnt 9B, 5A and 10B, were all shown to activate ion channel currents in PC3 cells.

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Wingless-related integration site (Wnt) comprises a diverse family of secreted signaling proteins (350–400 amino acids, 35-45 kDa), which act as close-range signaling molecules. Wnt signal activation initiates a complex downstream signal cascade in eukaryotic cells and is critical in the development of many diseases, including cancer.

It was possible to obtain both manual and automated patch clamp recordings of fragile and scarce Wnt proteins after a thorough optimization of the protein handling.

We highlight aspects of the handling of Wnt proteins optimized for APC testing, which could also be applied to other large molecules (e.g. peptide toxins, nanobodies, antibodies).

You can find all relevant Wnt signaling (and other large molecules) publications and posters here

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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.

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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

Sophion-Nanyang-papers

Two papers published by Nanyang Technological University Singapore on QPatch

Profs. Seow Theng Ong, George Chandy and colleagues at A*STAR and Nanyang Technological University, Singapore, have recently published two papers to share their research on ion channels and immunology using our QPatch solution.

In a multi-disciplinary collaboration spanning four continents, they published a Nature Microbiology paper contributing QPatch recordings of KCNJ15/Kir4.2 ion channels in monocyte immune cells. This work furthers our understanding of tuberculosis infection and clearance. The paper can be read here

The second paper generated cryo-EM structures of Kv1.3 ion channels with and without the Kv1.3 toxin peptide analogue dalazatide (ShK-186) bound. Kv1.3 ion channels are a key element in the activation of immune T-cells: by blocking them with dalazatide the over-activity seen in autoimmune diseases (e.g. psoriasis) can be reduced. Find the paper published in PNAS here

Sophion-poster-hIPSC-Göttingen

Big steps in cardiomyocyte action potential recordings on QPatch II

In a fruitful collaboration between Prof. Niels Voigt and scientist Fitzwilliam Seibertz of The University of Göttingen and our research scientist Kadla Røskva Rosholm, PhD, we have made great strides in overcoming the maturation and recording hurdles in the research of human induced pluripotent and stem cell (hiPSCs).

With improved culturing and induction techniques, the Voigt lab have generated consistently ‘matured’ hiPSC-derived CMs. These maturation developments married with significant advances in QPatch II current clamp recordings have led to high quality recordings and success rates.

Action potential recordings were made in physiological Ringer’s solutions on our QPatch II instrument without using fluoride or calcium ‘seal enhancing’ solutions. Our developments on automated patch clamping provides techniques for fast, efficient data generation allowing accurate biophysical and pharmacological characterisation of hiPSC-CMs.

This collaborative data was recently presented at the Biophysical Society meeting. See the poster here

Sophion-travel-and-research-grant

Sophion Travel & Research Grants for students and early career researchers

Sophion are pleased to announce two new grants supporting young scientists: travel & research grants.

We are looking for students (MSc or PhD) or early career scientists (within 5 years of BSc/MSc/PhD award). You are working in ion channels or related fields and you would like to present your work at Sophion’s Ion Channel Modulation Symposium. You could also have QPatch II or Qube384 data and want to tell your story at any international conference. Take this opportunity to make an application for our travel grant.

Alternatively, your postgraduate studies or early career lab research could be rocketed into the stratosphere by applying for our research grant. This will give you access to our platforms and experts in our labs across the world. Sophion’s research grant might be your ticket to completing a key finding for your thesis or strengthening your lab’s latest funding application.

 

For more info & application forms click here.

 

QPatch Compact semi-automated patch clamping

Introducing QPatch Compact – semi-automated patch clamping

With QPatch Compact, anyone can learn to patch-clamp in less than half an hour. The ready-to-use system offers the flexibility of manual patch clamp with the robustness and ease of use known from the QPatch and Qube automated patch clamping solutions.

QPatch Compact is a semi-automated patch-clamp solution enabling you to conduct up to 8 experiments at the same time, either synchronized to increase replicates or independent to increase information content in a short time.

The software helps you set up and analyze your experiments. All you must do is prepare the cells and handle the pipetting. QPatch Compact does the rest.

Imagine a benchtop instrument that you simply plug in and conduct your experiments without needing an antivibration table, micromanipulator, faraday cage, etc.

QPatch Compact gives you:

  • Stable recordings
  • Integrated system
  • Small footprint
  • Giga-seal on demand

Read more.