Nano-Immunology
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
Abstract
Research by my group aims to unravel nanoscopic changes at the molecular level in living cells to characterise important molecular processes on the cell membrane as well as inside the cell during immunological reactions. Because many cellular responses lead to changes so subtle at the molecular level, studying them requires us to not only observe them with a superior spatial resolution but also to reach a sensitivity that is able to monitor single molecules over time and space. We are using the newest and most powerful super-resolution far-field microscopes (such as STED, RESOLFT or PALM/STORM) to image and analyse cellular structures and protein-protein and protein-lipid interactions at a level of fine detail that until now has not been possible due to the limited spatial resolution of conventional optical far-field microscopes. By combining these super-resolution microscopy techniques with single-molecule sensitive detection methods (such as fluorescence correlation spectroscopy) and fast spatio-temporal tracking tools we are able to see complex dynamic processes otherwise invisible because of the lower power of conventional far-field microscopy. These molecular interactions play an important role in the immune response to infection and cancer and so we intend to use and further develop these advanced microscopy techniques and apply them to gather new insights in immunological research.
Technical Summary
Single-molecule super-resolution microscopy of membrane dynamics: Many cellular responses lead to subtle changes on the molecular level, demanding not only for a superior spatial resolution of the analyzing method but also for the sensitivity to monitor single molecules over time and space. The combination of super-resolution optical fluorescence STED microscopy with single-molecule sensitive fluorescence-detection tools such as Fluorescence Correlation Spectroscopy (FCS) as well as the fast spatio-temporal tracking of single labeled molecules (single-particle tracking, SPT) allows for the disclosure of complex dynamic processes otherwise impeded by the limited spatial resolution of conventional far-field microscopy. For example, STED-FCS or SPT offer us the possibility to gain novel insights into important cellular processes, such as lipid-lipid, lipid-protein, and protein-protein interactions and the formation of so-called “lipid-rafts” in the cellular plasma membrane. These molecular interactions play an important role in the cellular immune response. We will therefore apply and further develop the STED-FCS and SPT microscopy techniques to highlight important molecular processes on the plasma membrane as well as inside the cell during immunological reactions. For example, these techniques will be used to shed new light on different molecular pathways triggered at the cell surface and intracellularly during antigen presentation by dendritic cells and T cell activation.
Organisations
People |
ORCID iD |
Christian Eggeling (Principal Investigator) |
Publications
Koller T
(2017)
Rituximab capping triggers intracellular reorganization of B cells
in Matters
Kretzer C
(2021)
Ethoxy acetalated dextran-based nanocarriers accomplish efficient inhibition of leukotriene formation by a novel FLAP antagonist in human leukocytes and blood.
in Cellular and molecular life sciences : CMLS
Kühne M
(2023)
Analysis of HDACi-Coupled Nanoparticles: Opportunities and Challenges.
in Methods in molecular biology (Clifton, N.J.)
Kühne M
(2021)
Biocompatible sulfated valproic acid-coupled polysaccharide-based nanocarriers with HDAC inhibitory activity.
in Journal of controlled release : official journal of the Controlled Release Society
Lagerholm BC
(2017)
Convergence of lateral dynamic measurements in the plasma membrane of live cells from single particle tracking and STED-FCS.
in Journal of physics D: Applied physics
Lyman E
(2018)
From Dynamics to Membrane Organization: Experimental Breakthroughs Occasion a "Modeling Manifesto"
in Biophysical Journal
Lühr J
(2020)
Maturation of Monocyte-Derived DCs Leads to Increased Cellular Stiffness, Higher Membrane Fluidity, and Changed Lipid Composition
in Frontiers in Immunology
Mobarak E
(2018)
How to minimize dye-induced perturbations while studying biomembrane structure and dynamics: PEG linkers as a rational alternative.
in Biochimica et biophysica acta. Biomembranes
Pereno V
(2017)
Electroformation of Giant Unilamellar Vesicles on Stainless Steel Electrodes.
in ACS omega
Pinkwart K
(2019)
Nanoscale dynamics of cholesterol in the cell membrane
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MC_UU_00008/1 | 01/04/2017 | 31/03/2023 | £2,738,000 | ||
MC_UU_00008/2 | Transfer | MC_UU_00008/1 | 01/04/2017 | 31/03/2023 | £1,821,000 |
MC_UU_00008/3 | Transfer | MC_UU_00008/2 | 01/04/2017 | 31/03/2023 | £2,257,000 |
MC_UU_00008/4 | Transfer | MC_UU_00008/3 | 01/04/2017 | 31/03/2023 | £1,459,000 |
MC_UU_00008/5 | Transfer | MC_UU_00008/4 | 01/04/2017 | 31/03/2023 | £1,346,000 |
MC_UU_00008/6 | Transfer | MC_UU_00008/5 | 01/04/2017 | 31/03/2023 | £1,660,000 |
MC_UU_00008/7 | Transfer | MC_UU_00008/6 | 01/04/2017 | 31/03/2023 | £401,000 |
MC_UU_00008/8 | Transfer | MC_UU_00008/7 | 01/04/2017 | 31/03/2024 | £2,876,000 |
MC_UU_00008/9 | Transfer | MC_UU_00008/8 | 01/04/2017 | 31/03/2023 | £2,568,000 |
MC_UU_00008/10 | Transfer | MC_UU_00008/9 | 01/04/2017 | 31/03/2023 | £2,060,000 |
MC_UU_00008/11 | Transfer | MC_UU_00008/10 | 01/04/2017 | 31/03/2023 | £1,477,000 |