NTase Products and Cyclic Nucleotide Signalling

This project aims to discover novel cyclic nucleotides and their signaling pathways in humans, focusing on uncharacterized nucleotidyltransferases to enhance immune responses and therapeutic options.

Subsidie
€ 1.755.873
2024

Projectdetails

Introduction

Survival of a cell depends on its ability to receive and process information coming from the environment. Second messengers are the key transmitters of information that rapidly amplify the signal inside the cell. Cyclic nucleotides (CNs) are the most diversified category of second messengers and are found in all organisms modulating diverse pathways.

Background on Cyclic Nucleotides

CNs are best studied in bacteria, where they have a variety of biological functions. In humans, the only described cyclic di-nucleotide is cGAMP, which elicits an antiviral immune response. cGAMP is rapidly emerging as a promising drug candidate in, e.g., cancer immunotherapy.

Hypothesis

I hypothesize that additional CNs contribute to yet uncharacterized pathways in humans and my aim is to discover novel CNs and their signalling pathways. CNs are synthesized by nucleotidyltransferases (NTases) and many human NTases remain uncharacterized due to the lack of activity in the absence of the cognate ligand.

Project Aims

This project aims to reveal the molecular function of uncharacterized NTases and to discover novel CN signalling pathways in humans in immune and non-immune-related areas of biology.

Objectives

  1. Objective ❶: Focus on the activation of as yet uncharacterized NTases.
  2. Objective ❷: Identify CN signalling pathways involved in immune responses and beyond.

Expected Outcomes

The proposed experiments will provide me with candidates and precedence for CN signalling in humans other than cGAMP. The concept that yet uncharacterized CNs are involved in immune signalling as well as other pathways is highly innovative.

Significance

Together, the well-studied activities in bacteria and the overall conservation of NTases in humans further support the fundamental involvement of CN signalling in humans. My proposed research will open up conceptually new modes of regulation in human biology, reveal novel signalling pathways, and in the long term contribute to new therapeutic options using CNs as drugs.

Financiële details & Tijdlijn

Financiële details

Subsidiebedrag€ 1.755.873
Totale projectbegroting€ 1.755.873

Tijdlijn

Startdatum1-3-2024
Einddatum28-2-2029
Subsidiejaar2024

Partners & Locaties

Projectpartners

  • TECHNISCHE UNIVERSITAET MUENCHENpenvoerder

Land(en)

Germany

Vergelijkbare projecten binnen European Research Council

ERC STG

MANUNKIND: Determinants and Dynamics of Collaborative Exploitation

This project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery.

€ 1.497.749
ERC STG

Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressure

The UnderPressure project aims to investigate how mechanical constraints from 3D crowding affect cell proliferation and signaling in various organisms, with potential applications in reducing cancer chemoresistance.

€ 1.498.280
ERC STG

Uncovering the mechanisms of action of an antiviral bacterium

This project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function.

€ 1.500.000
ERC STG

The Ethics of Loneliness and Sociability

This project aims to develop a normative theory of loneliness by analyzing ethical responsibilities of individuals and societies to prevent and alleviate loneliness, establishing a new philosophical sub-field.

€ 1.025.860

Vergelijkbare projecten uit andere regelingen

ERC ADG

Functional Nanoscale Therapeutics

Develop functional hybrid nanoscale medicines to enhance intracellular delivery of mRNA and combat nanoscale pathogens, aiming for advanced therapies against diseases like cancer.

€ 2.499.796
ERC COG

Molecular and Functional Characterisation of Z-nucleic Acid-induced Signalling

This project aims to elucidate the mechanisms of ZBP1 activation by Z-nucleic acids to inform therapeutic strategies for modulating immune responses in autoinflammation, antiviral, and anticancer contexts.

€ 1.983.531
ERC ADG

Cyclic nucleotides as second messengers in plants

This project aims to establish cAMP and cGMP as key second messengers in plant signaling by developing optogenetic tools to manipulate their levels and explore their roles in various pathways.

€ 2.499.706
ERC POC

Targeted Immunocytokines by CaGing and local Release

This project aims to develop and evaluate a novel, locally activated innate immune therapy for cancer that minimizes systemic toxicity while enhancing treatment efficacy.

€ 150.000