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Synthetic Biology underpins advances in the bioeconomy

Biological systems - including the simplest cells - exhibit a broad range of functions to thrive in their environment. Research in the Imperial College Centre for Synthetic Biology is focused on the possibility of engineering the underlying biochemical processes to solve many of the challenges facing society, from healthcare to sustainable energy. In particular, we model, analyse, design and build biological and biochemical systems in living cells and/or in cell extracts, both exploring and enhancing the engineering potential of biology. 

As part of our research we develop novel methods to accelerate the celebrated Design-Build-Test-Learn synthetic biology cycle. As such research in the Centre for Synthetic Biology highly multi- and interdisciplinary covering computational modelling and machine learning approaches; automated platform development and genetic circuit engineering ; multi-cellular and multi-organismal interactions, including gene drive and genome engineering; metabolic engineering; in vitro/cell-free synthetic biology; engineered phages and directed evolution; and biomimetics, biomaterials and biological engineering.

Publications

Citation

BibTex format

@article{Toczek:2016:10.1016/j.bbadis.2016.08.019,
author = {Toczek, M and Zielonka, D and Zukowska, P and Marcinkowski, JT and Slominska, E and Isalan, M and Smolenski, RT and Mielcarek, M},
doi = {10.1016/j.bbadis.2016.08.019},
journal = {BBA - Molecular Basis of Disease},
pages = {2147--2157},
title = {An impaired metabolism of nucleotides underpins a novel mechanism of cardiac remodeling leading to Huntington's disease related cardiomyopathy},
url = {http://dx.doi.org/10.1016/j.bbadis.2016.08.019},
volume = {1862},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Huntington's disease (HD) is mainly thought of as a neurological disease, but multiple epidemiological studies havedemonstrated a number of cardiovascular events leading to heart failure in HD patients. Our recent studies showed anincreased risk of heart contractile dysfunction and dilated cardiomyopathy in HD pre-clinical models. This could potentiallyinvolve metabolic remodeling, that is a typical feature of the failing heart, with reduced activities of high energyphosphate generating pathways. In this study, we sought to identify metabolic abnormalities leading to HD-related cardiomyopathyin pre-clinical and clinical settings. We found that HD mouse models developed a profound deteriorationin cardiac energy equilibrium, despite AMP-activated protein kinase hyperphosphorylation. This was accompanied by areduced glucose usage and a significant deregulation of genes involved in de novo purine biosynthesis, in conversion ofadenine nucleotides, and in adenosine metabolism. Consequently, we observed increased levels of nucleotide catabolitessuch as inosine, hypoxanthine, xanthine and uric acid, in murine and human HD serum. These effects may be causedlocally by mutant HTT, via gain or loss of function effects, or distally by a lack of trophic signals from central nerve stimulation.Either may lead to energy equilibrium imbalances in cardiac cells, with activation of nucleotide catabolism plusan inhibition of re-synthesis. Our study suggests that future therapies should target cardiac mitochondrial dysfunction toameliorate energetic dysfunction. Importantly, we describe the first set of biomarkers related to heart and skeletal muscledysfunction in both pre-clinical and clinical HD settings.
AU - Toczek,M
AU - Zielonka,D
AU - Zukowska,P
AU - Marcinkowski,JT
AU - Slominska,E
AU - Isalan,M
AU - Smolenski,RT
AU - Mielcarek,M
DO - 10.1016/j.bbadis.2016.08.019
EP - 2157
PY - 2016///
SN - 0925-4439
SP - 2147
TI - An impaired metabolism of nucleotides underpins a novel mechanism of cardiac remodeling leading to Huntington's disease related cardiomyopathy
T2 - BBA - Molecular Basis of Disease
UR - http://dx.doi.org/10.1016/j.bbadis.2016.08.019
UR - http://hdl.handle.net/10044/1/39816
VL - 1862
ER -

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Work in the IC-CSynB is supported by a wide range of Research Councils, Learned Societies, Charities and more.