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    FEATURE

Replacing Radiolabeling with the SURFE²R N1 Platform

Customer Case Study with
Dr. Randy Stockbridge


Dr. Randy Stockbridge  (Assistant Professor at the University of Michigan) was one of the two SURFE²R N1 Grant Winners from 2018 where they won a SURFER N1 platform for a 6-month period. We asked Randy about her experience, established assays and future plans with the SURFE²R N1 instrument.

Click here to read the full Case Study.
 
"...we were quickly able to push the project in exciting, unexpected directions by screening a large family of structurally related substrates for transport. "

Dr. Randy Stockbridge about the SURFE²R N1 Platform
Win-a-SURFE²R-N1 2019
If you are working on transporters, and are curious about the SURFE²R N1 platform and how it could enable your research, you still have the opportunity to send your application to this year's "Win-a-SURFE²R-N1"-contest. Tell us what you would like to do if you had a SURFE²R N1 in your laboratory. Find more information on the contest here.

   NEWS   
US User Meeting, Dynamic Clamp, Job Exchange

Dynamic Clamp in Cardiac Safety


The dynamic clamp add-on for the Patchliner has been developed in a collaboration with Prof. Teun de Boer from UMC Utrecht in order to record stable action potentials from stem cell-derived cardiomyocytes (sc-CMs) with electrophysiological properties more representative of mature cardiomyocytes by introducing electrically modelled IK1 (see Goversen et al, 2018). With success rates in excess of 70% and routinely 7-8 cells recorded simultaneously, this feature could be the key for the use of sc-CMs in safety screening.

Insights from an expert: Read an interview with Nanion electrophysiologist and cardiac expert, Dr. András Horváth, about automated dynamic clamp on the Patchliner here.

Latest Publications


SyncroPatch 384PE:
Structure- and Ligand-Based Discovery of Chromane Arylsulfonamide Nav1.7 Inhibitors for the Treatment of Chronic Pain.
McKerrall S.J. et al., Journal of Medicinal Chemistry (2019)
Download here.

Patchliner:
Red Blood Cell Membrane Conductance in Hereditary Haemolytic Anaemias.
Petkova-Kirova P. et al., Frontier in Physiology (2019)
Download here.

Patchliner:
Discovery of BNC375, a Potent, Selective, and Orally Available Type I Positive Allosteric Modulator of α7 nAChRs.
Harvey A.J. et al., ACS Medicinal Chemistry Letters (2019)
Download here.

Port-a-Patch:
NMDA Receptor-Mediated Signaling Pathways Enhance Radiation Resistance, Survival and Migration in Glioblastoma Cells—A Potential Target for Adjuvant Radiotherapy.
Müller-Längle A. et al., Cancers (2019)
Download here.

Port-a-Patch:
Action of MK‐7264 (Gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation.
Richards D. et al., British Journal of Pharmacology (2019)
Download here.

Port-a-Patch:
Molecular understanding of calcium permeation through the open Orai channel.
Liu X.. et al., PLOS Computational Biology (2019)
Download here.

Port-a-Patch:
Breaching the Barrier: Quantifying Antibiotic Permeability across Gram-Negative Bacterial Membranes.
Cama J. et al., Journal of Molecular Biology (2019)
Download here.

Vesicle Prep Pro:
An Intrinsically Disordered Region in OSBP Acts as an Entropic Barrier to Control Protein Dynamics and Orientation at Membrane Contact Sites.
Jamecna D. et al., Developmental Cell (2019)
Download here.


Vesicle Prep Pro:
Self‐Assembly of Giant Unilamellar Vesicles by Film Hydration Methodologies.
Rideau E. D. et al., Advanced Biosystems (2019)
Download here.

Snapshot of the Month

 
Graduate Student Chris Macdonald at the SURFE²R N1 platform in Dr. Randy Stockbridge's laboratory at the University of Michigan, Ann Arbor, MI, USA.  It looks like some serious transporter activity going on there, at least what one can tell from the screen. Keep it going, Chris!

Last chance to register for the US User Meeting!

 
Mark your calendar for the upcoming US User Meeting, which will be held on the 28th - 29th May in Boston, USA.
If you are interested in presenting your work as an oral presentation or poster, please send an e-mail to Rodolfo Haedo.
We have a great line-up of speakers, including Prof. David Weaver, Prof. Jorge Contreras, Prof. Al George, Dr. David Dalrymple, Dr. May Fern Toh, Dr. Marc Rogers and many more! Find out more here and book your place today!

Assay.Works to offer services on the SURFE²R 96SE 


Dr. Ralf Schwandner (Assay.Works):  "We are excited to work with Nanion on providing SURFE²R transport assays for compound profiling and screening. As a CRO specializing in assay services, we offer comprehensive support for your SURF²ER-based transporter research: Cell line engineering, production of cell membranes, assay development, and screening. Using our contact-free dispensing platform, we can prepare sample dilutions from your own compounds, or provide access to our bioactive (5k) or diversity screening (150k) libraries, respectively."
Dr. Niels Fertig (Nanion): "We are delighted that Assay.Works is engaging with Nanion to offer services on the SURFE²R technology. Personally, I am very glad to see that our powerful transporter assay technology will be available via a CRO for our customers!"

Visit Assay Works webpage here.  

Job Exchange

 
Nanion Technologies, Inc. (Livingston, USA): Application Scientist. Click here for more information.

Victor Chang Cardiac Research Institute (Sydney, Australia): Lead Scientist - Cell Phenotyping. Click here for more information.

Mark Your Calendar


15. - 17. May 2019:
The Reci VII. 2019 Conference
(Cáceres, Spain). Meet Conrad Weichbrodt and Maria Giustina Rotordam.

16. - 20. June 2019:
The 7th Internatonal Ion Channel Conference
(Hangzhou, China). Meet Andy Di.

17. - 20. June 2019:
18th Annual World Preclinical Congress
(Boston, USA). Meet Ronald Knox.

   TOPIC   
Excitatory Amino Acid Transporter 3 (EAAT3)

Glutamate transporters - Controlling neuronal excitability


Glutamate is the major excitatory amino acid neurotransmitter in the mammalian brain. After glutamate release, it is important that the neurotransmitter is quickly removed from the extracellular space by cellular uptake to prevent excessive NMDA receptor stimulation which is toxic to neurons. Removal of the neurotransmitter is achieved by the excitatory amino acid transporters (EAAT). There are five genes in the mammalian genome encoding glutamate transporters EAAT 1-5 located on the SLC1 gene. EAAT3 (also known as excitatory amino acid carrier 1, EAAC1) is encoded by the SLC1A1 gene and is expressed exclusively by mature neurons. EAATs  are co-transporters, the stoichiometry of transport is 1 glutamate with 3 Na+ and 1 H+ moving into the cell to 1 K+ moving out of the cell.  
EAAT3: Critical in neuronal excitability and neuroprotection

EAAT3 is an important transporter not only for the local clearance of glutamate at synapses, but also as glutamate uptake into GABA-ergic neurons provides a precursor for the synthesis of GABA, the major inhibitory neurotransmitter in the mammalian CNS. In this way, EAAT3 has a role in regulating inhibitory synaptic transmission via GABA synthesis. EAAT3 also transports cysteine with a relatively high affinity and maximum rate of flux similar to that of glutamate. Cysteine is a precursor for the synthesis of glutathione, an antioxidant important for redox homeostasis in the CNS by reducing reactive oxygen species. EAAT3 has been implicated in a number of  diseases including epilepsy (e.g. hot water epilepsy), obsessive-cumpulsive disorder (OCD) and schizophrenia. It has also been suggested that EAAT3 may exert neuroprotective effects given it's role in cysteine uptake and glutathione synthesis and that it's dysfunction may play a role in certain neurodegenerative diseases such as Alzheimer's  disease, thereby providing potentially novel therapeutic targets for these conditions.

EAAT3: Recommended Assays, Cell Lines and Literature


Recommended assays:
  • SURFE2R N1 (Electrogenic transporter recordings): EC buffer exchange)
  • SURFE2R 96SE (96 parallel electrogenic transporter recordings): EC buffer exchange)

Read our two Application Notes and Poster from BPS18

Interested in more SURFE²R Data and Assays? Contact our experts directly here.
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