Focus Day

Tuesday April 11, 2023

9:45 am Chair’s Opening Remarks

Back to the Future with Ubiquitin

10:00 am Targeting Ubiquitination Zones

Synopsis

  • Spotlighting the relevance of ubiquitination zones for ligase drug discovery
  • Exploring ubiquitination when ubiquitin isn’t the target

10:30 am Sculpting the Ubiquitination Pattern to Ensure Efficient Proteasomal Degradation

Synopsis

  • Developing a better understanding of how different ubiquitin modifications influence degradation through the proteasome
  • Characterizing how proteasome-bound deubiquitinases regulate the degradation process
  • Identifying substrates dependent on deubiquitinase activity for degradation

11:00 am Showcasing the Mechanisms of Substrate Ubiquitination by the Anaphase-Promoting Complex/Cyclosome

  • Nicholas Brown Assistant Professor, University of North Carolina - Chapel Hill

Synopsis

  • Investigating the Anaphase-Promoting Complex/Cyclosome (APC/C) as a master regulator of cell cycle control
  • Dissecting the mechanisms of processive polyubiquitination using cryo-EM
  • Uncovering new substrate binding modes and discussing potential implications for other RING E3s

11:30 am PANEL DISCUSSION: Bridging the Knowledge Gap from Ubiquitination to the Proteasome

Synopsis

  • Progressing our knowledge gap from ubiquitination to the proteasome
  • Identifying whether deubiquitination has occurred and how this impinges on degradation expression levels

12:15 pm Afternoon Networking Break

Navigating E3 Ligase Protein Biology & Structural Functions

1:15 pm Supercharging Our Understanding of E3 Ligases to Enable Substrate Identification

Synopsis

  • Harnessing structural biology information of your target ligase to overcome the complexity of studying ligases
  • Considering the location of your ligase in the context of the cell cycle and the flexibility of the protein
  • Identifying substrates using pull-down assays to check for signatures

1:45 pm INTERACTIVE ROUNDTABLE DISCUSSION

Synopsis

Considering Dynamic Molecular Movement in AI Structures

  • Weighing the benefits of static crystal modeling versus current AI/ML approaches to achieving dynamic molecular structures
  • What are the current limitations to AI modeling techniques/technologies?

Understanding Structural Dynamics for Large & Moving Molecules

  • Design high-resolution structures for large and complex molecules
  • Detailing why large molecules have notoriously been difficult to achieve crystal structures for
  • Are we any closer with recent technological advancements?

2:45 pm Afternoon Networking Break

3:15 pm Uncovering the Biology & Drug-Ability of an Orphaned Ubiquitin E3 Ligase

Synopsis

  • Characterizing an E3 ligase from a structural biology perspective and pathophysiology
  • Exploring the downstream effects of degradation of the ligase through protein expression analyses
  • Identifying the endogenous substrate for small molecule decision making

3:45 pm Performing Cryo-EM Analyses of the DDB1 CRBN Apo Complex to Demonstrate Functional Insights of Allosteric Regulation of Cereblon

4:15 pm Chair’s Closing Remarks & End of Focus Day

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