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Development of a nanobody-based, slide-free approach for 3D-Histological analysis of the spatial tumor microenvironment using lightsheet imaging

Project description

3D histological analysis for detailed tumour microenvironment

Rapid and precise evaluation of biopsied tissues is critical for accurate disease diagnosis. While traditional 2D histopathology often lacks spatial resolution, 3D histopathology offers slide-free imaging and enhanced volumetric insights into critical structures. The ERC-funded 3D-SpatiOmics project aims to revolutionise cancer histology through an innovative nanobody-based approach, utilising non-destructive volumetric light-sheet microscopy. This cutting-edge technique will provide detailed spatial descriptions of the tumour microenvironment, enhancing tumour sample diagnoses and improving patient outcomes. The project will develop nanobodies for whole-mount tissue staining of the immune system and tumour markers. By employing cleavable fluorescent dyes and click chemistry, it will enable multiple rounds of multiplex staining on the same sample, paving the way for advanced diagnostic phenotyping.

Objective

For histopathological analysis and subsequent diagnosis of diseased tissues a rapid, accurate histopathological and genetic analysis of biopsied tissues are essential. However, traditional 2-dimensional slide-based histopathological analysis does not represent spatial tissue structures and molecular targets sufficiently, which aggravates an accurate and spatial analysis of tissue, a detailed description of the tumor microenvironment as well as patient stratification.
To overcome these limitations, I propose an innovative, nanobody-based 3D-histopathology approach using non-destructive volumetric lightsheet-microscopy. This approach bears the potential to revolutionize the way pathological analysis of tumor samples are done. In comparison to conventional 2D-pathology, non-destructive 3D-histopathology allows rapid slide-free histological imaging of an entire tissue sample, volumetric analysis of diagnostic relevant structures such as immune cells, vessels and an improved spatial analysis of cell distribution relevant to study e.g. the microenvironment.
To achieve this, we will generate nanobodies for improved wholemount tissue staining of the immune system as well as tumor-relevant markers. By labelling nanobodies with cleavable fluorescent dyes using click chemistry and integration of linkers for stoichiometric and directed labelling, we will be able to perform several rounds of multiplex staining of the identical sample and therefore provide cutting-edge diagnostic phenotyping of the specimen. Due to non-destructive nature of the optical-sectioning methodology, the sample is available for downstream applications such as molecular diagnostics of the previously imaged specimen.
In summary, this innovative project holds the great potential to revolutionize cancer histology by providing a spatial and detailed description of the tumor microenvironment, improving diagnosis of tumor samples and consequently patient stratification and outcome.

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2024-POC

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Host institution

CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
Chariteplatz 1
10117 Berlin
Germany

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Region
Berlin Berlin Berlin
Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (1)

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