IMX Seminar Series - Molecular Bionics
Event details
| Date | 07.11.2022 |
| Hour | 13:15 › 14:15 |
| Speaker | Prof. Giuseppe Battaglia, IBEC, Barcelona, Spain |
| Location | |
| Category | Conferences - Seminars |
| Event Language | English |
Soft materials for Phenotypic (nano)medicines
The central dogma in biological interactions and its application to drug design states that the higher the drug or ligand affinity (i.e. the most negative binding energy) to its cognate receptor, the higher its ability to target cells or tissues expressing the same receptor. However, such a maximal selectivity at the single molecules imposes that high-affinity ligands target indiscriminately any cells expressing the given receptor. The chemical nature of biological units extends beyond single molecules. As biomolecules combine into single cells, the number of configurations increases so much that we can confidently say that each cell of our body is different from the other. Perhaps we do not need to dissect the complexity of the single cell down to the quantum level to create more selective drugs. Still, we need to upgrade our molecular design to include more holistic effects to distinguish biological targets more precisely. In the last decade, we have assessed biological targets’ internal state energetic configurations matching them with complementary multivalent units to favour selective associations based on multiple bonds. We have borrowed statistical and soft matter physics tools to address this challenge. We know [1] that multivalent units interact via the collective effect of the single affinities (or avidity) and association changes with receptors or ligand numbers not linearly, giving rise to entropy-driven interactions. This unique nature means that if we combine low-affinity ligands, we can have association only when receptors are high in numbers, effectively targeting cells that overexpress the desired receptor. We have proposed a new theoretical framework and proven it experimentally [2-4], demonstrating that the overall interaction combines the specific ligand/receptor bonds with mean-field repulsive potential from steric effects. Using such a formalism, I will show that we can adapt soft materials such as block copolymers to molecularly engineer multivalent units that can be used as carriers to deliver drugs more efficiently or exert specific actions and become drugs.
[1] F.J. Martinez-Veracoechea and D. Frenkel, ‘Designing super selectivity in the multivalent nano-particle binding’. PNAS, 108, 10963 (2011)
[2] X. Tian, S. Angioletti-Uberti, and G. Battaglia, 'On the design of precision nanomedicines’. Sci. Adv., 2020. 6, eaat0919.
[3] M. Liu, A. Apriceno, A., M. Sipin, E. Scarpa, L. Rodriguez-Arco, A. Poma, G. Marchello, G. Battaglia and S. Angioletti-Uberti ‘Combinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions. Nat Commun. 11, 4836 (2021)
[4] S. Acosta-Gutiérrez, D. Matias, M. Avila-Olias, V. M. Gouveia, E. Scarpa, J. Forth, C. Contini, A. Duro-Castano, L. Rizzello, and G. Battaglia ‘A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting’ ACS Cent. Sci. , 8, 7, 891–904, (2022)
The central dogma in biological interactions and its application to drug design states that the higher the drug or ligand affinity (i.e. the most negative binding energy) to its cognate receptor, the higher its ability to target cells or tissues expressing the same receptor. However, such a maximal selectivity at the single molecules imposes that high-affinity ligands target indiscriminately any cells expressing the given receptor. The chemical nature of biological units extends beyond single molecules. As biomolecules combine into single cells, the number of configurations increases so much that we can confidently say that each cell of our body is different from the other. Perhaps we do not need to dissect the complexity of the single cell down to the quantum level to create more selective drugs. Still, we need to upgrade our molecular design to include more holistic effects to distinguish biological targets more precisely. In the last decade, we have assessed biological targets’ internal state energetic configurations matching them with complementary multivalent units to favour selective associations based on multiple bonds. We have borrowed statistical and soft matter physics tools to address this challenge. We know [1] that multivalent units interact via the collective effect of the single affinities (or avidity) and association changes with receptors or ligand numbers not linearly, giving rise to entropy-driven interactions. This unique nature means that if we combine low-affinity ligands, we can have association only when receptors are high in numbers, effectively targeting cells that overexpress the desired receptor. We have proposed a new theoretical framework and proven it experimentally [2-4], demonstrating that the overall interaction combines the specific ligand/receptor bonds with mean-field repulsive potential from steric effects. Using such a formalism, I will show that we can adapt soft materials such as block copolymers to molecularly engineer multivalent units that can be used as carriers to deliver drugs more efficiently or exert specific actions and become drugs.
[1] F.J. Martinez-Veracoechea and D. Frenkel, ‘Designing super selectivity in the multivalent nano-particle binding’. PNAS, 108, 10963 (2011)
[2] X. Tian, S. Angioletti-Uberti, and G. Battaglia, 'On the design of precision nanomedicines’. Sci. Adv., 2020. 6, eaat0919.
[3] M. Liu, A. Apriceno, A., M. Sipin, E. Scarpa, L. Rodriguez-Arco, A. Poma, G. Marchello, G. Battaglia and S. Angioletti-Uberti ‘Combinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions. Nat Commun. 11, 4836 (2021)
[4] S. Acosta-Gutiérrez, D. Matias, M. Avila-Olias, V. M. Gouveia, E. Scarpa, J. Forth, C. Contini, A. Duro-Castano, L. Rizzello, and G. Battaglia ‘A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting’ ACS Cent. Sci. , 8, 7, 891–904, (2022)
M. Liu, A. Apriceno, A., M. Sipin, E. Scarpa, L. Rodriguez-Arco, A. Poma, G. Marchello, G. Battaglia and S. Angioletti-Uberti ‘Combinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions. Nat Commun. 11, 4836 (2021)
S. Acosta-Gutiérrez, D. Matias, M. Avila-Olias, V. M. Gouveia, E. Scarpa, J. Forth, C. Contini, A. Duro-Castano, L. Rizzello, and G. Battaglia ‘A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting’ ACS Cent. Sci. , 8, 7, 891–904, (2022)
Bio: Prof Beppe (short for Giuseppe) Battaglia, is an ERC Consolidator grantee and ICREA Research Professor. In 2019 Beppe was appointed senior group leader at the Institute of Bioengineering of Catalonia part of the Barcelona Institute of Science and Technology. Beppe is an honorary professor in the Department of Chemistry at the University College London (UCL) and visiting professor at West China Hospital Sichuan University. Beppe holds a Laurea in Chemical Engineering from Univerisity of Palermo and PhD in Physical Chemistry from University of Sheffield. Before moving to Barcelona, Beppe held positions at UCL (Professor of Molecular Bionics 2013-2022) and the University of Sheffield (Professor of Synthetic Biology (2011-2013), Senior Lecturer (2009-2011) and Lecturer (2006-2009) in Bionanotechnology. Beppe was awarded the 2009 HFSP Young Investigator award jointly with Adam Engler (UCSD), the 2011 APS/IoP Polymer Physics Exchange Award Lecture, the 2011 GSK Emerging Scientist Award, the 2012 Award for special contribution to Polymer Therapeutics, the 2014 RSC Thomas Graham Award Lecture, and the 2015 SCI/RSC McBain Medal for Colloid Science. Beppe was awarded a prestigious EPSRC Established Fellowship in 2016, an ERC Starting Grant in 2011, and an ERC Consolidator in 2018. Beppe was elected a fellow of the Royal Society of Biology, the Royal Society of Chemistry, and the Institute of Materials, Minerals & Mining. Beppe has published over 130 peer-reviewed papers and has been named inventor in 14 patents.
Beppe leads a strong team of chemists, physicists, mathematicians, engineers, and biologists who work alongside to design bionic units that mimic specific biological functions and introduce operations that do not exist in Nature. They apply a constructionist approach to mimic biological complexity in design principles to produce functional units from simple building blocks and their interactions; this approach is called Molecular Bionics. Beppe’s group is particularly interested in how molecules, macromolecules, viruses, vesicles, and whole cells traffic across our body barriers. The group combines novel microscopic tools with theoretical and computational physics to study biological transport from single molecules, cell membranes, and whole organisms. The acquired knowledge is thus translated to bioengineer novel nanomedicines, combining soft matter physics with synthetic chemistry.
S. Acosta-Gutiérrez, D. Matias, M. Avila-Olias, V. M. Gouveia, E. Scarpa, J. Forth, C. Contini, A. Duro-Castano, L. Rizzello, and G. Battaglia ‘A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting’ ACS Cent. Sci. , 8, 7, 891–904, (2022)
Bio: Prof Beppe (short for Giuseppe) Battaglia, is an ERC Consolidator grantee and ICREA Research Professor. In 2019 Beppe was appointed senior group leader at the Institute of Bioengineering of Catalonia part of the Barcelona Institute of Science and Technology. Beppe is an honorary professor in the Department of Chemistry at the University College London (UCL) and visiting professor at West China Hospital Sichuan University. Beppe holds a Laurea in Chemical Engineering from Univerisity of Palermo and PhD in Physical Chemistry from University of Sheffield. Before moving to Barcelona, Beppe held positions at UCL (Professor of Molecular Bionics 2013-2022) and the University of Sheffield (Professor of Synthetic Biology (2011-2013), Senior Lecturer (2009-2011) and Lecturer (2006-2009) in Bionanotechnology. Beppe was awarded the 2009 HFSP Young Investigator award jointly with Adam Engler (UCSD), the 2011 APS/IoP Polymer Physics Exchange Award Lecture, the 2011 GSK Emerging Scientist Award, the 2012 Award for special contribution to Polymer Therapeutics, the 2014 RSC Thomas Graham Award Lecture, and the 2015 SCI/RSC McBain Medal for Colloid Science. Beppe was awarded a prestigious EPSRC Established Fellowship in 2016, an ERC Starting Grant in 2011, and an ERC Consolidator in 2018. Beppe was elected a fellow of the Royal Society of Biology, the Royal Society of Chemistry, and the Institute of Materials, Minerals & Mining. Beppe has published over 130 peer-reviewed papers and has been named inventor in 14 patents.
Beppe leads a strong team of chemists, physicists, mathematicians, engineers, and biologists who work alongside to design bionic units that mimic specific biological functions and introduce operations that do not exist in Nature. They apply a constructionist approach to mimic biological complexity in design principles to produce functional units from simple building blocks and their interactions; this approach is called Molecular Bionics. Beppe’s group is particularly interested in how molecules, macromolecules, viruses, vesicles, and whole cells traffic across our body barriers. The group combines novel microscopic tools with theoretical and computational physics to study biological transport from single molecules, cell membranes, and whole organisms. The acquired knowledge is thus translated to bioengineer novel nanomedicines, combining soft matter physics with synthetic chemistry.
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Practical information
- General public
- Free
Organizer
- Maartje Bastings & Anirudh Natarajan
Contact
- Maartje Bastings & Anirudh Natarajan