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Diagnostic drug response-profiling using SLAMseq

Project description

Methodology for rapid determination of drug response

Being able to predict response to drug treatment would undoubtedly improve efficacy and reduce unnecessary treatments and drug-related side effects. To address this issue, the EU-funded SLAM-Dx project has developed a highly sensitive method (SLAMseq) for measuring newly synthesised and existing RNA in cells. The idea is to use this method to determine the effect of drug treatment associated with gene expression changes brought about by specific therapeutics. The speed, efficacy and precision of SLAMseq make it an ideal tool for guiding tailored anti-cancer treatment protocols in the clinic. Moreover, SLAMseq can be employed for high-throughput screening during the drug development process.

Objective

One of the greatest challenges today is to select the right drug for the right patient at the right time. A lack of diagnostic tools for predicting therapy response currently hampers patient-tailored treatment decisions in the clinic with severe implications for economy and – most importantly – patient survival.

Profiling transcriptional responses to drug treatment is a key method for probing the activity of targeted therapeutics and guiding their use in the clinic. A major limitation of established gene expression profiling techniques (such as microarrays and RNA-seq) is their limited time resolution precluding the distinction of direct from secondary transcriptional responses to drug therapy. This hampers their utility for deciphering drug action and guiding patient-tailored treatment decisions.

To overcome this problem, as part of an ERC-StG project (Systematic in-vivo analysis of chromatin-associated targets in leukemia, 336860) I have co-developed thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAMseq) as a rapid, robust and highly scalable method for the unbiased quantification of changes in mRNA production upon cell perturbations. Its unique features (low input cell numbers, short treatment-to-sample time, 1-day protocol library preparation in 96-well format) may qualify SLAMseq as the first method to probe the function, efficacy and selectivity of candidate therapeutics in primary (tumor) cells with unprecedented precision and on a large scale.

In this ERC-PoC project, I propose to establish technical and commercial proof-of-concept for SLAMseq’s application in preclinical and clinical drug development and optimization, and for patient-tailored treatment selection. Upon the successful proof-of-concept for SLAMseq’s application as diagnostic tool, SLAM-Dx has the potential to revolutionize translational research and personalised medicine in a variety of disease areas.

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-POC-LS - ERC Proof of Concept Lump Sum Pilot

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2019-PoC

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Host institution

FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
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
CAMPUS-VIENNA-BIOCENTER 1
1030 Wien
Austria

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Region
Ostösterreich Wien Wien
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 150 000,00

Beneficiaries (1)

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