Title of project or programme
Title of PI BH3- Only Proteins and Cellular Bioenergetic in the Control of Neuronal Survival and Cell Death: Role in Ischaemic Injury and Neurodegeneration
Principal Investigators of project/programme grant
Title Forname Surname Institution Country
Prof Jochen Prehn RCSI Ireland
Address of institution of lead PI
Institution Royal College of Surgeons in Ireland
Street Address 123 St Stephen’s Green
City Dublin
Postcode 2
Country
  • Ireland
Source of funding information

Science Foundation Ireland

Total sum awarded (Euro)

3471112.00

Start date of award

01-01-2009

Total duration of award in months

60

The project/programme is most relevant to
  • Neurodegenerative disease in general
Keywords

Neuronal Apoptosis, Excitotoxicity, Ca2+ Mediated Cell Death, ER
Stress, Proteasomal Stress, Ischemic Stroke, Neurodegeneration, BH3 Only
Proteins, BIM, PUMA, Mitochondria, Bioenergetics, Computational Biology, Systems Biology

Research abstract in English

The proposed programme will investigate key mechanisms underlying neuronal survival
and cell death in response to ischemic brain injury and during chronic neurodegeneration.
Based on previous research, we will investigate the role of pro-apoptotic BH3 Only
Proteins and cellular and mitochondrial bioenergetics in cell death and cell survival
decisions in response to neuronal Ca2+ overloading, endoplasmic reticulum stress,
proteasomal inhibition, and oxygen/glucose deprivation. These studies will be conducted
using established neuronal cell culture and organotypic slice culture systems, and key
findings will be translated into appropriate animal models. Building on our expertise
and previous investments in single-cell analysis, quantitative microscopy, and
computational biology, we aim to identify key decision and intervention points using both
hypothesis-driven and systems-driven research approaches. These investigations will
generate novel therapeutic targets and prognostic tools for drug discovery, which could
ultimately benefit the treatment of ischemic brain injury, chronic neurodegeneration, and
potentially other disorders of inappropriate cell death signalling.

Lay summary

Stroke and age-related brain disorders are leading causes of death and disability
which, with increasing life expectancy in Ireland, impose a growing economic and
societal burden. Current treatment regimes are limited in their effectiveness, partially
due to a lack of understanding of why nerve cells die or survive during brain injury.
This research programme tackles this important question by investigating a family of
genes that mediate stress-induced cell death, and by addressing the role of reduced
energy supply during brain injury. The programme involves an established collaboration
with SIEMENS engineers who will bring essential computational approaches into this
research programme that facilitate the analysis of biological networks, and accelerate the
identification of new targets for future therapy. The research programme also allows for the
development and dissemination of new, Irish born, technology by integrating the activities
of LUXCEL Biosciences, a pioneer in oxygen sensing technologies, into the research
programme.

In which category does this research fall?
  • Basic research

Types: Investments > €500k
Member States: Ireland
Diseases: Neurodegenerative disease in general
Years: 2011
Database Categories: N/A
Database Tags: N/A

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