Archive for the ‘Themed Collections’ Category

HOT article: picking out the protease – simultaneous determination of multiple protease activities

The enzymes Matrix metalloproteinases (MMPs) and A Disintegrin and Metalloproteinases (ADAMs) are two related protease families which play key roles in physiological processes. MMPs are involved in processes such as development, angiogenesis and tissue remodeling, whilst ADAMs mediate various cellular behaviour. Many useful methodologies currently exist to study metalloproteinases but none simultaneously allow for direct, non-invasive, multiplex, real-time measurements of specific protease activity.

Proteolytic Activity Matrix Analysis (PrAMA) is an integrated experimental measurement and mathematical analysis framework, developed by Douglas A. Lauffenburger et al., Massachusetts Institute of Technology, in an attempt to address this issue.

This method uses panels of FRET-substrates to infer a dynamic, quantitative and specific profile of MMP and ADAM proteolytic activities and by utilising predetermined signatures, from purified enzymes, it is possible to deconvolute signals from complex protease mixtures to ascertain specific protease activity. PrAMA appears to be able to distinguish closely related enzymes with a high accuracy and can do so even when there is  unknown background proteolytic activity present.

Lauffenburger et al. believe that this has the potential to be used in areas ranging from systems biology to in vitro inhibitor screening as well as other protease families.

Find out more about PrAMA by reading this HOT article, which is part of a forthcoming Integrative Biology themed issue in honour of Mina J. Bissell. Go on, it’s free for 4 weeks!

Proteolytic Activity Matrix Analysis (PrAMA) for simultaneous determination of multiple protease activities
Miles A. Miller, Layla Barkal, Karen Jeng, Andreas Herrlich, Marcia Moss, Linda G. Griffith and Douglas A. Lauffenburger
Integr. Biol., 2011, Advance Article
DOI: 10.1039/C0IB00083C

This article was published as part of a themed issue in honor of Mina J. Bissell.

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3D model to study breast cancer

Slice from the normal acini model after 12 days. Green: membrane, blue: nuclei, red: dividing cells

Scientists from the US have made a computational model of the formation of breast acini, the sac-like part of the milk-producing glands, to understand complex events occurring during the progression of breast cancer.

Jonathan Tang from the University of California, Berkeley, and colleagues, made a 3D model of acini formation, for the first time, to study how three different cell activities – apoptosis (programmed cell death), proliferation (cell division) and polarisation (organisation of cell components) – work together to form the tissue. In doing so, they hoped to determine how changes to these activities cause cancer.

‘We believed that such a model would enable us to identify which perturbations cause disorganised structures that resemble tumours, giving us a deeper insight into the complex nature of cancer,’ says Tang.

To read more, check out Elinor Richards’ Chemistry World article here or read the full paper online:

Phenotypic transition maps of 3D breast acini obtained by imaging-guided agent-based modeling
Jonathan Tang, Heiko Enderling, Sabine Becker-Weimann, Christopher Pham, Aris Polyzos, Chen-Yi Chen and Sylvain V. Costes
Integr. Biol., 2011
DOI: 10.1039/c0ib00092b

This article was published as part of a themed issue in honor of Mina J. Bissell.

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HOT review: Apoptotic cell signalling in cancer progression and therapy

Read this HOT review article by Jessica Plati, Octavian Bucur and Roya Khosravi-Far from Harvard Medical School.

The review, which comes highly recommended by the referees,  highlights the role and therapeutic use of various apoptosis regulators, such as in the BCL-2 family proteins, inhibitor of apoptosis proteins, and the FLICE-inhibitory protein. The review also discusses the importance of preclinical models utilizing three dimensional systems and genetically engineered mouse models in validation of novel apoptosis-based cancer therapeutics.

Apoptotic cell signaling in cancer progression and therapy
Jessica Plati, Octavian Bucur and Roya Khosravi-Far
Integr. Biol., 2011, Advance Article
DOI: 10.1039/C0IB00144A, Review

This article was published as part of a themed issue in honor of Mina J. Bissell.

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Issue 2 – Synthetic biology themed issue now available online

We are delighted to bring you this small but perfectly formed themed issue on synthetic biology, guest edited by board member John McCarthy.

You can read his editorial online here, where he discusses the relationship between synthetic biology and systems biology and his hopes for the field.

The issue contains a diverse range of articles, from computational tools for system design and modelling to virus-based nanoparticles as carriers for metals or chemical compounds:

Multi-scale modelling and simulation in systems biology
Joseph O. Dada and Pedro Mendes
Integr. Biol., 2011, 3, 86

Computational design approaches and tools for synthetic biology
James T. MacDonald, Chris Barnes, Richard I. Kitney, Paul S. Freemont and Guy-Bart V. Stan
Integr. Biol., 2011, 3, 97

DNA assembly for synthetic biology: from parts to pathways and beyond
Tom Ellis, Tom Adie and Geoff S. Baldwin
Integr. Biol., 2011, 3, 109

Chemically-coupled-peptide-promoted virus nanoparticle templated mineralization
Alaa A. A. Aljabali, Sachin N. Shah, Richard Evans-Gowing, George P. Lomonossoff and David J. Evans
Integr. Biol., 2011, 3, 119

Complex function by design using spatially pre-structured synthetic microbial communities: degradation of pentachlorophenol in the presence of Hg(ii)
Hyun Jung Kim, Wenbin Du and Rustem F. Ismagilov
Integr. Biol., 2011, 3, 126

Fluid-shear-stress-induced translocation of aquaporin-2 and reorganization of actin cytoskeleton in renal tubular epithelial cells
Kyung-Jin Jang, Hye Sung Cho, Do Hyun Kang, Won Gyu Bae, Tae-Hwan Kwon and Kahp-Yang Suh
Integr. Biol., 2011, 3, 134

In vivo sodium concentration continuously monitored with fluorescent sensors
J. Matthew Dubach, Edward Lim, Ning Zhang, Kevin P. Francis and Heather Clark
Integr. Biol., 2011, 3, 142

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