SLAS2016 Short Courses

Affinity-based, Biophysical Methods for Screening and Mechanistic Studies

• Gain an overview of the most relevant biochemical biophysics/ label-free technologies for screening and lead finding/characterization. Learn how this toolbox of novel technologies helps advancing target-based drug discovery projects.
• Focus: biophysics assay applications that allow for the detection, quantification and qualification of ligand/protein binding events with suitability for screening, hit follow-up, and characterization.
• Learn the tailored strategies of the technologies, their key applications in drug discovery projects, and usage regarding their impact and limitations.
• Participate in active discussions about each technology in reference to their strengths, weaknesses, and practical application.

Who Should Attend:

• People interested in getting an overview about the current toolbox of affinity-based, biophysical methods currently applied in drug discovery)
• Experts in one of the fields (biophysical technologies) that want to learn more about other approaches
• Project leaders that want to understand what technologies suit their needs
• Technology providers that want to gain more insight into the needs of typical users

How You Will Benefit From This Course:

Get a broad overview about what is available and state of the art in the field

• Comprehend which technology best fits to individual project needs and scientific questions
• Learn about typical applications and "best practice" as well as limitations and practical considerations
• Understand how the biophysics technologies relate to each other and how they augment and synergize with data from other approaches
• Be able to predict for a project which technology (or combinations thereof) serves best in a typical drug discovery flowchart along with its placement

Course Topics:

Overview of the most relevant biochemical biophysics/ label-free technologies for screening and lead finding

• Main technologies discussed in more detail: Mass Spectrometry; NMR; Calorimetry (DSC, ITC); SPR; Interferometry; Resonance Waveguide Grating (aka Corning Epic); thermal protein denaturation and aggregation assays (DSF aka Thermofluor, DSLS aka Stargazer); Dynamic Light Scattering; Microscale Thermophoresis (NanoTemper).
• Understand which technology fits best to answer specific questions in drug discovery projects
• Grasp how biophysics can support assay development for screening

Course Pre-Reading Requirements:

• General introduction into affinity-based methods and their application in DD:
  . 2010 Nov;5(11):1095-107. doi: 10.1517/17460441.2010.524641. Epub 2010 Oct 7.

  Affinity-based screening techniques: their impact and benefit to increase the number of high quality leads.
  
  . 2010 Oct;172(1):142-57. doi: 10.1016/j.jsb.2010.06.024. Epub 2010 Jul 4.

  Affinity-based, biophysical methods to detect and analyze ligand binding to recombinant proteins: matching high information content with high throughput.
  , , ,

• ITC:
  . 2001 Oct;11(5):560-6.

  Direct measurement of protein binding energetics by isothermal titration calorimetry.
  ,

• NMR:
  . 2013 Jun;56(2):65-75. doi: 10.1007/s10858-013-9740-z. Epub 2013 May 18.

  Fragment-based drug discovery using NMR spectroscopy.
  , , .

• SPR:
  2006;12(31):3999-4021.

  Biomolecular interaction analysis in drug discovery using surface plasmon resonance technology.
  ,

• MS:
  2007 Oct;11(5):518-26. Epub 2007 Oct 10.

  Affinity selection-mass spectrometry screening techniques for small molecule drug discovery.
  , , , , .

• MST:

  . 2013 Mar;59(3):301-15. doi: 10.1016/j.ymeth.2012.12.005. Epub 2012 Dec 24.

  Microscale thermophoresis quantifies biomolecular interactions under previously challenging conditions.
  ¹, , , , , , , , , , , , , , , , .

• RWG:
  2015;1278:139-52. doi: 10.1007/978-1-4939-2425-7_8.

  Resonant waveguide grating for monitoring biomolecular interactions.
  ¹, .

• DLS:
  . 2015 Jan 13;31(1):3-12. doi: 10.1021/la501789z. Epub 2014 Jul 31.

  Making sense of Brownian motion: colloid characterization by dynamic light scattering.
  , , .

• DSF:
  . 2012 Apr;10(2):128-36. doi: 10.1089/adt.2011.0390. Epub 2011 Nov 8.

  Thermal denaturation assays in chemical biology.
  , , .

Instructor Bios:

Christine Genick / Novartis Institutes for BioMedical Research Basel, Center for Proteomic Chemistry Dr. Christine Genick has been working since 2000 in the field of label free technologies, not only on the development of technologies for screening, but also in the utilization of these approaches for lead finding in drug discovery. In 2009, Chris joined the Screening Sciences Group at Novartis, as a laboratory head in charge of biophysical hit validation for HTS, FBS, and focused screen follow-up. In 2015, she joined the Structural Biophysics Group and in conjunction with her current responsibilities, she is the Core Biophysics Technology Representative, which entails searching for new applications, technologies, and approaches to detect small molecule binding interactions with target proteins. Chris also heads the SPR Core Facility for NIBR and manages various types of exploratory projects involving biophysics.

Stefan Geschwindner / AstraZeneca R&D Mölndal, Discovery Sciences, Structure & Biophysics Dr. Stefan Geschwindner has already during his Ph.D. worked with label-free technologies, predominantly with NMR to elucidate protein structures. Stefan joined the Astra Structural Chemistry Laboratory as a Senior Research Scientist in 1998 with focus on protein production and characterization applying a variety of biophysical methods. Before moving into his current role as Principal Scientist in Biophysics at AstraZeneca in 2006, he had different roles as Team leader in Protein Engineering as well as Delivery leader for Neuroscience. During this last decade, Stefan has frequently applied biophysical methods to facilitate the mechanistic understanding of protein-ligand interactions and to enable fragment-based lead generation approaches. He has the shared responsibility and an excellent track record for developing and implementing new biophysical approaches to aid early lead finding activities.