Designing Therapeutic Proteins From Natural Effectors
Event details
| Date | 28.03.2024 |
| Hour | 10:00 › 11:00 |
| Speaker | Prof. Julia Shifman, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem (IL) |
| Location | Online |
| Category | Conferences - Seminars |
| Event Language | English |
BIOENGINEERING SEMINAR
Abstract:
Protein-protein interactions (PPIs) are critical for all cellular functions. Abnormal PPIs are often the underlying cause of various diseases, making the inhibition of these interactions an appealing approach for therapeutic intervention. We develop PPI inhibitors from natural protein effectors, which already bind to their targets and are non-toxic and non-immunogenic, making them ideal for drug design. However, natural effectors often lack specificity, interacting with multiple proteins. We enhance effector binding specificity for a particular target by introducing affinity-enhancing mutations and supplying them with extended loops that interact with non-conserved regions on their target proteins. Using a combination of computational and experimental approaches, we successfully developed inhibitors for two established cancer targets, matrix metalloproteinases and Ras, showing high affinity and specificity in vitro and in cellular assays. This strategy is universal and can be applied to target any disease-associated PPI.
Bio:
Julia Shifman is a Professor of Biophysics and Biochemistry and the Chair of the Department of Biological Chemistry at the Hebrew University of Jerusalem. Dr. Shifman has been working in the field of protein design from its inception, and she was among the first to apply computational design to protein-protein interactions. Her group is focused on developing computational and experimental methods for studying of protein evolution and designing therapeutic proteins that disrupt protein-protein interactions. Dr. Shifman obtained her PhD in Biophysics from the University of Pennsylvania and performed her postdoctoral training at Caltech.
Zoom link for attending remotely: https://epfl.zoom.us/j/68647279829
Abstract:
Protein-protein interactions (PPIs) are critical for all cellular functions. Abnormal PPIs are often the underlying cause of various diseases, making the inhibition of these interactions an appealing approach for therapeutic intervention. We develop PPI inhibitors from natural protein effectors, which already bind to their targets and are non-toxic and non-immunogenic, making them ideal for drug design. However, natural effectors often lack specificity, interacting with multiple proteins. We enhance effector binding specificity for a particular target by introducing affinity-enhancing mutations and supplying them with extended loops that interact with non-conserved regions on their target proteins. Using a combination of computational and experimental approaches, we successfully developed inhibitors for two established cancer targets, matrix metalloproteinases and Ras, showing high affinity and specificity in vitro and in cellular assays. This strategy is universal and can be applied to target any disease-associated PPI.
Bio:
Julia Shifman is a Professor of Biophysics and Biochemistry and the Chair of the Department of Biological Chemistry at the Hebrew University of Jerusalem. Dr. Shifman has been working in the field of protein design from its inception, and she was among the first to apply computational design to protein-protein interactions. Her group is focused on developing computational and experimental methods for studying of protein evolution and designing therapeutic proteins that disrupt protein-protein interactions. Dr. Shifman obtained her PhD in Biophysics from the University of Pennsylvania and performed her postdoctoral training at Caltech.
Zoom link for attending remotely: https://epfl.zoom.us/j/68647279829
Practical information
- Informed public
- Free
Organizer
- Prof. Bruno Correia, Laboratory of Protein Design and Immunoengineering (LPDI), Institute of Bioengineering (IBI), École polytechnique fédérale de Lausanne (EPFL)
Contact
- Ms. Suzanne Balharry, Laboratory of Protein Design and Immunoengineering (LPDI), Institute of Bioengineering (IBI), École polytechnique fédérale de Lausanne (EPFL)