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BPS 18

February 17 - February 21

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The Biophysical Society Annual Meeting

As science becomes increasingly interdisciplinary, the Biophysical Society Annual Meeting continues its long-held reputation for bringing together leading scientists from the all over the world who work at the interface of the life, physical, and computational sciences.

The dynamic five-day Meeting provides attendees with opportunities to share their latest unpublished findings and learn the newest emerging techniques and applications.

Despite its nearly 6,500 attendees, the Meeting is noted for maintaining its “small meeting” feel beginning with the Saturday subgroup symposia, which allow attendees to meet within their scientific communities. It is also known for its vitality, demonstrated by the over 900 highly interactive daily poster presentations, the more than 500 speakers selected from submitted abstracts, the many career development programs for those working in academia, industry, and agencies throughout the world, and its advocacy and education programs.

Join Cellular Dynamics for an Exhibitor Presentation

Sunday, Feb 18 | 10:30 am – 12:00 pm | Exhibit Presentation Room 6

Using Human iPSC-derived Cell-Types in Novel Functional Assays, Disease Modeling and Drug Discovery

The availability of donor-specific induced pluripotent stem (iPS) cells, coupled with gene-editing techniques is enabling new insights into the molecular basis and mechanisms of human disease. Join us as we describe how Cellular Dynamics’ cryopreserved iPSC-derived cell types have been used to develop disease models with innate or introduced mutations.

10:30 am: Dr. Leonard Kaczmarek from Yale University will begin the talks by describing the use of stem cells in understanding mechanisms of ataxias and epilepsy, highlighting human iPSC-derived neurons harboring mutations in the KCNT1 Slack channel.

11:00 am: Dr. Kile Mangan from Cellular Dynamics International will follow with a talk on utilizing novel functional assays with high-definition multielectrode arrays (HD-MEAs: MaxWell Biosystems) to uncover phenotypic differences in neurons harboring single-nucleotide disease mutations (alpha synuclein A53T Parkinson’s Disease) or in normal control following pharmacological perturbation.

11:30 am: ​Recent advances in cardiac tissue engineering have increased significantly cell functional across electrophysiological, Ca2+ handling, and contractility. The third presentation of this session will discuss these advances and provide exemplar laboratory case studies highlighting the increased functionality and experimental implementation.

Poster Presentation

Poster Board Number: B424

iPSC-Derived Neurons Harboring a Known Epilepsy Mutation Provide a “Disease-in-a-Dish” Capabiluity that Displays Established and Novel Epileptic Phenotypes

Kile P. Mangan1, Imran Quraishi2, Yalan Zhang2, Michael McLachlan1, Benjamin Meline1, Chris McMahon1, Elisabeth Enghofer1, Christian Kannemeier1, Eugenia Jones1, Leonard Kaczmarek2

1. Cellular Dynamics International, Madison, WI, USA
2. Yale University, New Haven, CT, USA.

Abstract: Epilepsy is a disturbance in the electrical activity of the brain that effects 65 million individuals, one-third of whom live with intractable epilepsy. A portion of this population is accounted for by single-gene epilepsy disorders resulting from mutations within sodium, potassium or inhibitory channels. Here we investigate the Slack gene (KCNT1), which encodes a sodium-activated potassium channel that is very widely expressed in the brain. Mutations in the KCNT1 gene in humans presents with autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE), a disease marked by brief but violent seizures during sleep and results in devastating effects on intellectual function. Advances in personalized medicine are crucial to combating these types of disabling disorders.
Central to the vision of personalized medicine is the technology of induced pluripotent stem cells (iPSCs). iPSC technology provides a platform to expand our understanding of how single-gene mutations manifest disease states. This ability provides unprecedented access to in vitro models of all-types of neurological disorders. The approach presented here illustrates how the “disease-in-a-dish” iPSC-technology can be leveraged for phenotypic characterization and screening, and how to navigate these types of investigations into the drug development space.
Human cortical neurons harboring the KCNT1 {P924L} single-gene mutation werer engineered and generated, as well as where the isogenic wild-type control match. Using protein (Western Blots) and functional evaluations (patch-clamp and multi-electrode array), we illustrate iPSC-derived cortical neurons harboring the KCNT1 {P924L} mutation recapitulate a well characterized ‘gain-of-function’ ionotropic cellular-level fingerprint without altered cellular Slack-protein levels. We further present novel neural-network level, hyper-active phenotypes associated with this KCNT1 mutation and use selective pharmacology to reverse the aberrant phenotypes. Collective results illustrate how human iPSC-derived neurons can successfully be harnessed within the personalized medicine space.

Details

Start:
February 17
End:
February 21
Website:
https://www.biophysics.org/2018meeting/Home/tabid/7117/Default.aspx

Organizer

Biophysical Society
Website:
https://www.biophysics.org/

Venue

Moscone Center
747 Howard St.
San Francisco, CA 94103 United States
Website:
http://www.moscone.com/site/do/index