[TALK 11] Thermal Shift Methods & High Throughput Screening - Antonia Turberville & Laura Usselmann

Value of the Information & Strength of the Argument

The talk provides valuable practical insights into the application of thermal shift assays in an industrial HTS setting. The speakers clearly explain the principles, advantages, and limitations of each method, supported by real-world examples from their screening campaigns. The argumentation is solid, as they justify their choices (e.g., using SYPRO Orange, focusing on stabilizers) based on empirical observations and practical constraints. They also acknowledge the challenges, such as protein consumption and detergent sensitivity, and discuss emerging technologies like optical folding to address them. The presentation is well-structured and informative, making it a useful resource for researchers in drug discovery.

Scientific Rigor, Source Quality, Title Accuracy

The talk is scientifically rigorous, with detailed methodological descriptions and practical considerations. The speakers reference their own experience and mention the origins of CETSA (National University of Singapore and Karolinska Institute), but they do not cite specific publications. The description provides links to AstraZeneca’s R&D page and the LMB’s website, which are relevant but not directly to the methods discussed. The title accurately reflects the content, covering both thermal shift methods and their application in HTS. The presentation is from the MRC Laboratory of Molecular Biology, a reputable institution, and the speakers are industry experts, lending credibility to the content.

The title accurately reflects the content, which covers thermal shift methods (DSF, nanoDSF, CETSA) and their application in high throughput screening.

8/10

The talk is delivered by industry experts from AstraZeneca's high throughput screening team, providing detailed methodological insights and practical considerations. The content is based on their extensive experience, but it is not peer-reviewed and represents expert opinion rather than original research.

Markers derived by PSI from the transcript: the creator did not define chapters.

• 00:00Introduction to high throughput screening at AstraZeneca
• 03:00Overview of HTS workflow and portfolio evolution
• 07:00Principle of thermal shift assays and introduction to DSF
• 10:00Dye-based DSF: assay setup, dye selection, and considerations
• 15:00Automation of DSF using Certus and QuantStudio 7
• 20:00Data analysis: first derivative, Boltzmann equation, and handling biphasic curves
• 25:00Examples of hit compounds and data interpretation
• 30:00Introduction to nanoDSF and its applications
• 35:00CETSA: principle and detection methods
• 40:00Isothermal CETSA with NanoLuciferase and large-scale screening
• 45:00Comparison of DSF and CETSA methods

• AstraZeneca R&D — Referenced as the company's research and development page, providing context for their work.
• MRC Laboratory of Molecular Biology — The host institution for the talk, providing credibility and context.
• LMB 2025/26 Solving Problems with Molecular Techniques series — The playlist containing this talk and related videos.

• AstraZeneca R&D — The company's R&D page supports the industrial context of the talk.
• MRC Laboratory of Molecular Biology — The host institution's website provides background on the LMB's research focus.

• www.linkedin.com
• www.youtube.com