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Deciphering the microRNA response to hypoxia

Objective

Maintaining oxygen homeostasis is an essential requirement for all metazoa. Oxygen is required for efficient generation of energy, however, as oxygen levels decrease (hypoxia), cells mount a variety of adaptive responses. Each cell in the body can sense and respond to hypoxia, yet the molecular mechanisms that regulate these responses are only beginning to be delineated. Hypoxia plays crucial roles in the pathophysiology of cancer, neurological dysfunction, myocardial infarction and lung disease. Therefore, the goal of the proposed research is to better understand how cells sense and adapt to hypoxia. To this end, I am using the powerful genetic model of Caenorhabditis elegans to identify novel molecular mechanisms required for oxygen homeostatic responses.
A critical regulator of hypoxic responses in all cell types is the conserved hypoxia-inducible factor (HIF-1). In response to a hypoxic insult, HIF-1 transcriptionally regulates a wide variety of target genes to facilitate adaptation. Recent studies indicate that in addition to the canonical HIF-1 pathway, microRNAs (miRNAs) play important roles in hypoxic response mechanisms. miRNAs are regulatory molecules that predominantly repress protein production of their target genes, however, their roles in hypoxic adaptation are poorly understood. I recently found that specific phylogenetically conserved miRNAs are regulated by hypoxia in C. elegans; and that the function of these miRNAs is required for survival of animals in low oxygen conditions. This is truly an emerging field of science and I expect to make groundbreaking discoveries in the regulation of hypoxic and metabolic responses by miRNAs, which will improve our understanding of many disease processes.
The proposed research will 1) analyze the functional roles of specific miRNAs in hypoxic responses and 2) utilize immunoprecipitation, bioinformatics and genetic screening combined with state-of-the-art deep sequencing technology to identify novel miRNA targets required for adaptation to hypoxia.
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Principal Investigator

Roger David John Pocock (Dr.)

Host institution

KOBENHAVNS UNIVERSITET

Address

Norregade 10
1165 Kobenhavn

Denmark

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 478 508

Principal Investigator

Roger David John Pocock (Dr.)

Administrative Contact

Kirsten Lange (Ms.)

Beneficiaries (1)

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KOBENHAVNS UNIVERSITET

Denmark

EU Contribution

€ 1 478 508

Project information

Grant agreement ID: 260807

Status

Closed project

  • Start date

    1 November 2010

  • End date

    31 October 2015

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 1 478 508

  • EU contribution

    € 1 478 508

Hosted by:

KOBENHAVNS UNIVERSITET

Denmark