Program

SLAS2017 Short Courses

Affinity-Based, Biophysical Methods for Screening and Mechanistic Studies: How to Effectively Use a Growing Biophysical Toolbox to Find and Characterize Chemical Leads

The course will be delivered in two parts, the first section focusing on theoretical aspects in a seminar format and the following section dealing with practical applications in an open and active discussion format.

In the first section, you will receive a series of brief high-level presentations concerning the biophysical theory behind each technology and their application in lead finding, hit validation as well as more in depth mechanistic studies. This will enable you to gain an rapid overview of the most relevant biophysics/ label-free technologies for screening and lead finding/characterization.

In the second section you will be presented with some challenges how to effectively apply those technologies by looking at a range of common scenarios from different phases of lead discovery. This will include fragment-based drug discovery, hit validation and confirmation, in-depth hit characterization and support of HTS assay development. Making use of an active and open discussion forum, you, as a part of a team, will thereby gain further insight about the usage, impact, and limitations of each biophysical technology.

Who Should Attend:

How You Will Benefit From This Course?

Course Topics:

Course Pre-Reading Requirements:

General introduction into affinity-based methods and their application in DD:
(articles which describe how the approaches work, caveats, and a summary of their impact)

  1. Affinity-based screening techniques: their impact and benefit to increase the number of high quality leads
    Bergsdorf, Christian ; Ottl, Johannes
    Expert opinion on drug discovery, November 2010, Vol.5(11), pp.1095-107
    Identifier: E-ISSN: 1746-045X ; PMID: 22827747 Version:1 DOI: 10.1517/17460441.2010.524641
  2. Affinity-based, biophysical methods to detect and analyze ligand binding to recombinant proteins: Matching high information content with high throughput
    Holdgate, Geoff A. ; Anderson, Malcolm ; Edfeldt, Fredrik ; Geschwindner, Stefan
    Journal of Structural Biology, October 2010, Vol.172(1), pp.142-157
    Identifier: ISSN: 1047-8477 ; DOI: 10.1016/j.jsb.2010.06.024
  3. Twenty years on: the impact of fragments on drug discovery
    Daniel A. Erlanson ; Stephen W. Fesik ; Roderick E. Hubbard ; Wolfgang Jahnke ; Harren Jhoti
    Nature Reviews Drug Discovery, 2016 [Peer Reviewed Journal]
    Identifier: ISSN: 1474-1776 ; E-ISSN: 1474-1784 ; DOI: 10.1038/nrd.2016.109
  4. Integrating biophysics with HTS-driven drug discovery projects
    Folmer, Rutger H.A.
    Drug Discovery Today, March 2016, Vol.21(3), pp.491-498
    Identifier: ISSN: 1359-6446 ; DOI: 10.1016/j.drudis.2016.01.011
  5. Applications of Biophysics in High-Throughput Screening Hit Validation
    Genick, Christine Clougherty ; Barlier, Danielle ; Monna, Dominique ; Brunner, Reto ; Bé, Céline ; Scheufler, Clemens ; Ottl, Johannes
    Journal of biomolecular screening, June 2014, Vol.19(5), pp.707-14
    Identifier: E-ISSN: 1552-454X ; PMID: 24695619 Version:1 ; DOI: 10.1177/1087057114529462
  6. Biophysics in Drug Discovery: impact, challenges, and opportunities,
    Jean-Paul Renaud, Chun wa Chung, U. Helena Danielson, Ursula Egner, Michael Hennig, Roderick E. Hubbard, and Herbert Nar
    Nature Reviews, August 2016, (advanced on-line publication)

Background Information on each technology/approach:

Instructors:

Christine Genick
Novartis Institutes for BioMedical Research Basel, Center for Proteomic Chemistry

Dr. Christine Genick has been working since 2000 in the field of biophysics on the development of technologies and utilization of these approaches in drug discovery. In 2009, Chris joined 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 biophysical applications and approaches to detect small molecule binding interactions. Chris also heads the SPR Core Facility and manages various 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.