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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.
@article{Piotrowska:2017:10.1371/journal.pone.0180571,
author = {Piotrowska, I and Isalan, M and Mielcarek, ML},
doi = {10.1371/journal.pone.0180571},
journal = {PLOS One},
title = {Early transcriptional alteration of histone deacetylases in a murine model of doxorubicin-induced cardiomyopathy},
url = {http://dx.doi.org/10.1371/journal.pone.0180571},
volume = {12},
year = {2017}
}
TY - JOUR
AB - Doxorubicin is a potent chemotherapeutic agent that is widely-used to treat a variety of cancers but causes acute and chronic cardiac injury, severely limiting its use. Clinically, the acute side effects of doxorubicin are mostly manageable, whereas the delayed consequences can lead to life-threatening heart failure, even decades after cancer treatment. The cardiotoxicity of doxorubicin is subject to a critical cumulative dose and so dosage limitation is considered to be the best way to reduce these effects. Hence, a number of studies have defined a “safe dose” of the drug, both in animal models and clinical settings, with the aim of avoiding long-term cardiac effects. Here we show that a dose generally considered as safe in a mouse model can induce harmful changes in the myocardium, as early as 2 weeks after infusion. The adverse changes include the development of fibrotic lesions, disarray of cardiomyocytes and a major transcription dysregulation. Importantly, low-dose doxorubicin caused specific changes in the transcriptional profile of several histone deacetylases (HDACs) which are epigenetic regulators of cardiac remodelling. This suggests that cardioprotective therapies, aimed at modulating HDACs during doxorubicin treatment, deserve further exploration.
AU - Piotrowska,I
AU - Isalan,M
AU - Mielcarek,ML
DO - 10.1371/journal.pone.0180571
PY - 2017///
SN - 1932-6203
TI - Early transcriptional alteration of histone deacetylases in a murine model of doxorubicin-induced cardiomyopathy
T2 - PLOS One
UR - http://dx.doi.org/10.1371/journal.pone.0180571
UR - https://doi.org/10.1371/journal.%20pone.0180571
UR - http://hdl.handle.net/10044/1/49471
VL - 12
ER -