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Transcriptional networks in glucose sensing

Transcriptional networks in glucose sensing

Objective

Glucose is key source of nutritional energy and raw material for biosynthetic processes. Maintaining glucose homeostasis requires a regulatory network that functions both in the systemic level through hormonal signaling and locally at the intracellular level. Insulin signalling is the main hormonal mechanism involved in maintaining the levels of circulating glucose through regulation of cellular glucose intake and metabolism. While the signalling pathways mediating the effects of insulin have been thoroughly studied, the transcriptional networks downstream of insulin signalling are not comprehensively understood. In addition to insulin signalling, intracellular glucose sensing mechanisms, including transcription factor complex MondoA/B-Mlx, have recently emerged as important regulators of glucose metabolism. In the proposed project we aim to take a systematic approach to characterize the transcriptional regulators involved in glucose sensing and metabolism in physiological context, using Drosophila as the main model system. We will use several complementary screening strategies, both in vivo and in cell culture, to identify transcription factors regulated by insulin and intracellular glucose. Identified transcription factors will be exposed to a panel of in vivo tests measuring parameters related to glucose and energy metabolism, aiming to identify those transcriptional regulators most essential in maintaining glucose homeostasis. With these factors, we will proceed to in-depth analysis, generating mutant alleles, analysing their metabolic profile and physiologically important target genes as well as functional conservation in mammals. Our aim is to identify and characterize several novel transcriptional regulators involved in glucose metabolism and to achieve a comprehensive overview on how these transcriptional regulators act together to achieve metabolic homeostasis in response to fluctuating dietary glucose intake.

Principal Investigator

Ville Ilmari Hietakangas (Dr.)

Host institution

HELSINGIN YLIOPISTO

Address

Yliopistonkatu 3
00014 Helsingin Yliopisto

Finland

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 496 930

Principal Investigator

Ville Ilmari Hietakangas (Dr.)

Administrative Contact

Javier Arévalo (Dr.)

Beneficiaries (1)

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HELSINGIN YLIOPISTO

Finland

EU Contribution

€ 1 496 930

Project information

Grant agreement ID: 281720

Status

Closed project

  • Start date

    1 January 2012

  • End date

    28 February 2017

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 1 496 930

  • EU contribution

    € 1 496 930

Hosted by:

HELSINGIN YLIOPISTO

Finland