Research Interests
Design of Synthetic Organelles and Biomolecular Condensates with Tunable Properties
Inspired by membraneless organelles (biomolecular condensates) formed through liquid-liquid phase separation (LLPS) of proteins and nucleic acids, we develop minimalistic biomolecular condensates that integrate intra- and intermolecular order/disorder features.
To achieve this, we design peptides, DNA, and RNA as condensate building blocks, enabling their phase separation into liquid droplets via LLPS. Through systematic sequence design, we aim to elucidate the molecular interactions driving condensate formation and engineer condensates with tunable physicochemical and material properties.
References:
1. Baruch Leshem, A., Sloan-Dennison, S., Massarano, T., Ben-David, S., Graham, D., Faulds, K., Gottlieb, H. E., Chill, J. H., and Lampel, A. Biomolecular condensates formed by designer minimalistic peptides. Nature communications, 2023, 14(1), 421. https://doi.org/10.1038/s41467-023-36060-8
2. Netzer, A., Leshem, A.B.,Veretnik, S., Edelstein I., and Lampel, A., Regulation of Peptide Liquid–Liquid Phase Separation by Aromatic Amino Acid Composition. Small, 2024. https://doi.org/10.1002/smll.202401665
3. Lampel, A. Biology-inspired supramolecular peptide systems. Chem 2020, 6, 1222-1236. *Invited Perspective. https://doi.org/10.1016/j.chempr.2020.03.005
​4. Ulijn, R.V. and Lampel, A. Order/disorder in protein and peptide-based biomaterials. Israel Journal of Chemistry, 2019, 60, 1129-1140. https://doi.org/10.1002/ijch.201900051
Designed Condensates as Delivery Platforms​
We design single- and multi-component condensates formed via liquid-liquid phase separation (LLPS) of peptides, nucleic acid polymers, or glycan polymers, serving as delivery platforms.
One of our key objectives is to understand the factors influencing payload encapsulation within these designed condensates. We study a diverse range of payloads, from small hydrophobic molecules and drugs to large macromolecules such as enzymes, growth factors, and antibodies.
Our ultimate goal is to develop stable and reliable platforms for targeted payload delivery into specific tissues.
References:
1. Katzir, I., Haimov, E., and Lampel, A., Tuning the Dynamics of Viral-Factories-Inspired Compartments Formed by Peptide–RNA Liquid–Liquid Phase Separation. Advanced Materials 2022, 2206371. https://doi.org/10.1002/adma.202206371
Peptide Materials for Biosensing Applications
Leveraging our expertise in peptide design and condensate engineering, we aim to develop sensitive diagnostic tools based on peptide materials, including peptide gels and condensates.
Recently, we demonstrated that peptide/RNA condensates can function as both microreactors and optical sensors for tyrosinase activity. Additionally, we developed a detection system by encapsulating carbon dots within peptide condensates.
Building on this foundation, we continue to advance peptide-based detection platforms, expanding their applications in diagnostics and sensing.
References:
1. Netzer, A., Kaztir, I., Leshem, A.B., Weitman, M. and Lampel, A., Emergent properties of melanin-inspired peptide/RNA condensates. Proceedings of the National Academy of Sciences, 120(44), e2310569120, 2023. https://doi.org/10.1073/pnas.2310569120
2. Gaash, D., Dewan, S., Baruch Leshem, A., Jaiswal, K. S., Jelinek, R., and Lampel, A., Modulating the optical properties of carbon dots by peptide condensates. Chemical Communications, 59, 12298 - 12301, 2023. https://doi.org/10.1039/D3CC03945E
3. Wulf, V., Bichachi, E., Hendler-Neumark, A., Massarano, T., Leshem, A. B., Lampel, A.*, and Bisker, G.*, Multicomponent System of Single-Walled Carbon Nanotubes Functionalized with a Melanin-Inspired Material for Optical Detection and Scavenging of Metals. Advanced Functional Materials 2022, 2209688. https://doi.org/10.1002/adfm.202209688
Phase-Separated Materials for Biocatalysis and Green Chemistry
One of our key research efforts focuses on developing phase-separated materials to regulate enzymatic and organic reactions. By designing synthetic condensates with systematically tunable chemical compositions using minimalistic LLPS-promoting peptides, we aim to elucidate how chemical composition, physical properties, and material characteristics influence reaction rate, conversion, and condensate reactivity.
Our peptide LLPS-based approach for condensate formation offers a novel route for sustainable synthesis in an organic solvent-free aqueous environment, aligning with green chemistry principles. Ultimately, these designed condensate libraries can serve as bio-friendly microenvironments for the regulation of enzymatic and organic reactions, including applications in drug synthesis.
References:
1. Harris, R., Berman, N, and Lampel, A., Charge-Mediated Interactions Affect Enzymatic Reactions inPeptide Condensates. ChemSystemsChem, e202400055, 2024. https://doi.org/10.1002/syst.202400055
2. Harris, R., Veretnik, S., Dewan, S., Leshem, A.B.,and Lampel, A., Regulation of enzymatic reactions by chemical composition of peptide biomolecular condensates. Communications Chemistry, 7(1), 90, 2024. https://doi.org/10.1038/s42004-024-01174-7
3. Massarano, T., Baruch Leshem, A., Weitman, M., and Lampel, A. Spatiotemporal Control of Melanin Synthesis in Liquid Droplets. ACS Applied Materials & Interfaces, 2022, 14, 20520-20527. https://doi.org/10.1021/acsami.1c21006