Archive for the ‘Review articles’ Category

Personalised treatment using systems biology – a review

Diagnosis and monitoring of many diseases usually involves testing for a specific disease-related molecular biomarkers from a small sample of tissue. Within a single tissue, the contents and functions of individual cells vary greatly. The regulation of the genome varies from cell to cell due to different regulatory mechanisms taking control.

If we could quantify the number of biomarker molecules per cell in a diseased sample this will lead to a more personalised approach to disease. For example, getting such a profile of all of the different cell types involved on one particular person’s leukaemia would reveal the different biomarkers and their combinations that are resulting in the disease. Treatment could then be based on this detailed information.

Integrative Biology Editorial Board member Philip Day, University of Manchester, UK, and Ehsan Karimiani at the Mashhad University of Medical Sciences, Iran, present a complex but fascinating review of the steps that are being made towards personalisation of disease monitoring made possible by such a quantitative systems medicine approach to genetic biomarker analysis.

The focus is on quantitative single cell measurements for haematological malignancy monitoring. This review includes: 

  1. Sample preparation
  2. The multidisciplinary future of molecular diagnostics
  3. Nucleic acid profiling for diagnostics
  4. Gene expression profiling of single cells for diagnostics
  5. The role of minaturisation and microfluidics in PCR

The review concludes with a look at what may be possible in the future, with Karimiani and Day emphasising that current practices need to change drastically before this personalised approach can become a reality.

For more in depth explanation, read the review in full:

Personalised treatment of haematological malignancies through systems medicine based on single molecules in single cells
Ehsan Ghayoor Karimiani and Philip Day
DOI: 10.1039/C3IB20258E

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Single-molecule imaging’s insights into the puzzling components of cells

Iva Tolić-Nørrelykke and colleagues at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, have written a fascinating tutorial review on how single-molecule imaging is revealing the pieces of cellular jigsaw puzzles.

single-molecule imaging

They see the cell as a dynamic puzzle, with pieces being created, destroyed and changing their interactions all the time. These pieces can now be viewed in vivo using various techniques in single-molecule microscopy with high precision. The measurement of intracellular reactions can also be carried out in order to build models of intricate cellular processes.

As well as a brief chronological look at the developments in single-molecule microscopy and useful short explanations of the different techniques as a glossary, this review includes: 

  1. Appropriate labelling methods
  2. Total Internal Reflection Fluorescence (TIRF) in vivo
  3. Widefield microscopy for a low signal-to-noise ratio and Selective Plane Illumination Microscopy (SPIM)
  4. Fluorescence Speckle Microscopy using tubulin and Photoactivation with a specific wavelength
  5. Mapping lots of individual molecules inside a cell using super-resolution fluorescence methods
  6. Single-molecule FRET for studying conformational change

They emphasise that due to the complications arising inside a cell, the molecules must be resolved spatially in different ways according to the different techniques and they discuss which techniques are best suited to which types of investigation. Single-molecule imaging is compared with ensemble methods and the goal of measuring a large number of molecular events simultaneously in real time is discussed.

Learn more about the potential of single-molecule imaging in the full Tutorial review:

Single-molecule imaging in vivo: the dancing building blocks of the cell
Miguel Coelho, Nicola Maghelli and Iva M. Tolić-Nørrelykke
DOI: 10.1039/C3IB40018B

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Mechanobiology, stem cells, predicting chemoresistance, retinopathy analysis and chemoattractant effects all in Integrative Biology Issue 3, online now!

The outside front cover of this month’s issue showcases a Frontier article from Yubing Sun and Jianping Fu at the University of Michigan on mechanobiology and stem cells, which was also featured in a recent blog post. They highlight just how vital understanding of the mechano-sensitive properties of stem cells is to being able to explore the abilities of stem cells. As a cover article, this is now free to access for 6 weeks*:

Mechanobiology: a new frontier for human pluripotent stem cells
Yubing Sun and Jianping Fu
DOI: 10.1039/C2IB20256E


This issue contains an important contribution from the team of Douglas Lauffenburger, Chair of the Editorial Board, at MIT, USA, in which they demonstrate the ability to characterise quantitative data on phenotypic behaviour of individual endothelial cells in response to angiogenesis signalling and relate it to overall population behaviour.  They show that the behaviour of microvascular endothelial cells in a single population is heterogeneous and cannot be assumed to be the same for all cells in a given condition.

Endothelial cell phenotypic behaviors cluster into dynamic state transition programs modulated by angiogenic and angiostatic cytokines
Tharathorn Rimchala, Roger D. Kamm and Douglas A. Lauffenburger
DOI: 10.1039/C2IB20090B


There are a number of other HOT articles, including:

An integrative network inference approach to predict mechanisms of cancer chemoresistance
Paola Lecca
DOI: 10.1039/C2IB20205K

Read the recent blog post on this article here!

Non-dimensional analysis of retinal microaneurysms: critical threshold for treatment
Elishai Ezra, Eliezer Keinan, Yossi Mandel, Michael E. Boulton and Yaakov Nahmias
DOI: 10.1039/C3IB20259C

Read the recent blog post on this article here!

Convolution of chemoattractant secretion rate, source density, and receptor desensitization direct diverse migration patterns in leukocytes
Yana Wang and Darrell J. Irvine
DOI: 10.1039/C3IB20249F

 For the full online contents list, click here!

 *Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

A HOT Frontier article: the mechanobiology of human pluripotent stem cells

The promise of human pluripotent stem cells in disease treatment, drug screens and regenerative medicine remains an exciting area of biological research, with new technologies and techniques helping to increase our understanding. The intracellular signalling processes and the extracellular conditions have always been HOT areas of research, but the mechanobiology influencing these pathways and reacting to these conditions is often overlooked.

stem cells, mechanobiologyIn this Frontier, Yubing Sun and Jianping Fu at the University of Michigan provide a discussion of the links currently being made between mechanobiology and the function of stem cells. They argue that understanding the sensitivity and reaction of hPSCs to stimuli in their environment is vital and that knowledge of the mechano-sensitive and mechano-responsive properties is central to that understanding.

Frontier articles are short reviews that focus on only the most recent research. This one includes:

  1. The role of cell adhesion molecules
  2. Influence of rigid and soft extracellular matrix
  3. Controllable mechanical forces
  4. Dissociation-induced apoptosis
  5. Innovative technologies and techniques

This Frontier is a fascinating read and it’s now free to access for the next 4 weeks*. Read it now by clicking the link:

Mechanobiology: a new frontier for human pluripotent stem cells
Yubing Sun and Jianping Fu
DOI: 10.1039/C2IB20256E

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Visualizing vascular disease – a critical review

intravital microscopy vesselsThe combination of intravital microscopy (IVM) and fluorescence imaging is the focus of this Critical Review. IVM allows us to look at biological processes as they happen and fluorescence imaging gives advantages of subcellular-resolution and detection capability.

Viviany Taqueti and Farouc Jaffer at Harvard Medical School, USA,  look at the advances in IVM technology and methods in this Critical Review, concentrating on its application in studying vascular disease. They include:

1.   Agents for molecular specificity
2.   Challenges of imaging vessel-based diseases atherosclerosis and thrombosis
3.   Unique in vivo biological insights obtained using IVM
4.   Brief comments on clinical application in the future

Intravital microscopy technology is going from strength to strength, providing us with increasing detail on in vivo processes. Find out more by reading this review in full:

High-resolution molecular imaging via intravital microscopy: illuminating vascular biology in vivo
Viviany R. Taqueti and Farouc A. Jaffer
DOI: 10.1039/C2IB20194A

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Issue 1 – Focus for 2013 and Cancer Nanotechnology Themed Issue

Welcome to a packed issue of Integrative Biology to begin the New Year!

Issue 1 begins with an editorial from Doug Lauffenburger, Chair of the Editorial Board in which he emphasises the focus of Integrative Biology in providing a ‘New Look at Biology’ and the interdisciplinary way in which our articles approach biological questions, opening up new lines of research and providing a platform for work that pushes known boundaries and conventions.

Our new look at biology
Douglas A. Lauffenburger
DOI: 10.1039/C2IB90056D


Guest Editor Piotr Grodzinski introduces the themed issue on Cancer Nanotechnology in his editorial, the aim of which is to present a select few articles that illustrate the ability of interdisciplinary work to answer biological problems, ultimately producing practical answers for clinical settings.

Themed issue on Cancer Nanotechnology
Piotr Grodzinski
DOI: 10.1039/C2IB90050E


The front cover of this themed issue features a Frontier Review from Steven Millward et al. providing a selective and critical look at the integration of in situ click chemistry with solid phase peptide libraries for ligand design.

In situ click chemistry: from small molecule discovery to synthetic antibodies
Steven W. Millward, Heather D. Agnew, Bert Lai, Su Seong Lee, Jaehong Lim, Arundhati Nag, Suresh Pitram, Rosemary Rohde and James R. Heath
DOI: 10.1039/C2IB20110K


On the inside front cover, a fascinating perspective by Alexander Stegh is highlighted on the progress towards personalized cancer nanomedicine and the large number of future challenges still faced to turn it into reality.

Toward personalized cancer nanomedicine – past, present, and future
Alexander H. Stegh
DOI: 10.1039/C2IB20104F


The work of the Nanotechnology Characterization Laboratory at the Frederick National Laboratory for Cancer Research, USA, is illustrated and described on this issue’s back cover. Read the perspective by Scott McNeil et al. here:

Common pitfalls in nanotechnology: lessons learned from NCI’s Nanotechnology Characterization Laboratory
Rachael M. Crist, Jennifer Hall Grossman, Anil K. Patri, Stephan T. Stern, Marina A. Dobrovolskaia, Pavan P. Adiseshaiah, Jeffrey D. Clogston and Scott E. McNeil
DOI: 10.1039/C2IB20117H


 

Issue 1 of 2013 is full of interesting editorials, reviews and primary research in the field of Cancer Nanotechnology, so why not take a look now here? Cover articles are free to access for 6 weeks!*

*Free access is provided to recognised institutions or to individuals through an RSC Publishing Personal Account. Registration is quick and easy at http://pubs.rsc.org/en/account/register.

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

A review – investigating microbial evolution

Vadim Mozhayskiy and Ilias Tagkopoulos at the UC Davis Genome Center, University of California Davis, USA, take a critical look at in vivo and in silico techniques that have been developed to study the evolution of microbial organisms and their sophisticated characteristics. They go even further and contemplate how these two separate approaches can be combined into one to gain more information for more complex environments.

This critical review includes 

  1. The advantages and challenges of controlled laboratory evolution of microorganisms
  2. The role of mathematical multiscale modelling and supercomputer simulation
  3. The balancing act of creating biologically realistic but computationally feasible in silico models

Read this interesting review in full:

Microbial evolution in vivo and in silico: methods and applications
Vadim Mozhayskiy and Ilias Tagkopoulos
DOI: 10.1039/C2IB20095C

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Issue 10 – tissue morphogenesis, natural killer cells and the NDRG4 gene

This month’s issue features work from Wesley Legant, Christopher Chen and Viola Vogel on the front cover.

The article uses microfabricated tissue gauges and Foerster Radius Energy Transfer (FRET) labeled biosensors to investigate the fibronectin assembly and matrix remodeling in a 3D microtissue model of tissue morphogenesis.

Force-induced fibronectin assembly and matrix remodeling in a 3D microtissue model of tissue morphogenesis
Wesley R. Legant, Christopher S. Chen and Viola Vogel
DOI: 10.1039/C2IB20059G


On the inside front cover, work from the USA is featured. In their article, Christopher Love and colleagues from the Massachusetts Institute of Technology and Harvard discuss their use of nanowells to monitor individual NK cell–target cell interactions.

Amongst other things, they found that lysis is most likely during an NK cell’s first encounter with a target.

Single-cell analysis of the dynamics and functional outcomes of interactions between human natural killer cells and target cells
Yvonne J. Yamanaka, Christoph T. Berger, Magdalena Sips, Patrick C. Cheney, Galit Alter and J. Christopher Love
DOI: 10.1039/C2IB20167D


The back cover this month features work from Dennis Hallahan, Jerry Jaboin and co-workers. In their article, they show that the down regulation of NDRG4 mRNA and protein expression in two aggressive cancer cell lines resulted in reduced cell survival, DNA fragmentation and G2-M cell cycle arrest.

The authors state the gene ‘may play a valuable role as a molecular target in [the] treatment’ of meningioma.

NDRG4, the N-Myc downstream regulated gene, is important for cell survival, tumor invasion and angiogenesis in meningiomas
Rama P. Kotipatruni, Daniel J. Ferraro, Xuan Ren, Robert P. Vanderwaal, Dinesh K. Thotala, Dennis E. Hallahan and Jerry J. Jaboin
DOI: 10.1039/C2IB20168B


The issue also includes a review from Jun Hu, Chunhai Fan and co-workers on nanomaterials-assisted PCR (nanoPCR) strategies, and their potential applications in genetic analysis (particularly gene typing and haplotyping) and diagnostics:

Genetic analysis with nanoPCR
Dun Pan, Lijuan Mi, Qing Huang, Jun Hu and Chunhai Fan
DOI: 10.1039/C2IB20076G

Read the rest of the issue here. Cover articles are free* to access for 6 weeks!

*Free access is provided to recognised institutions or to individuals through an RSC Publishing Personal Account. Registration is quick and easy at http://pubs.rsc.org/en/account/register.

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

A review: Genetic analysis with nanoPCR

In this review, researchers led by Jun Hu and Chunhai Fan at the Shanghai Institute of Applied Physics, China, focus on nanomaterials-assisted PCR (nanoPCR) strategies, and their potential applications in genetic analysis (particularly gene typing and haplotyping) and diagnostics.

The review covers:

1. Effects of nanomaterials on PCR
2. Proposed mechanisms for nanoPCR
3. Applications of nanoPCR

Read more in the full review:

Genetic analysis with nanoPCR
Dun Pan, Lijuan Mi, Qing Huang, Jun Hu and Chunhai Fan
DOI: 10.1039/C2IB20076G

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Building proteins brick by brick

In situ click chemistry: from small molecule discovery to synthetic antibodiesScientists have become adept at synthesising novel nucleotide sequences from scratch, but our comparative lack of understanding of how proteins are built has hampered development of new proteins to use in the lab or as a therapy. Novel peptides have to be designed via a screening process rather than de novo synthesis and proteins which are produced in vivo, such as antibodies, can suffer from batch variation.

In this review, Steven Millward and colleagues from California and Singapore explore how the screening technology Iterative Peptide In Situ Click Chemistry (IPISC) could not only allow for greater control over the peptide synthesis process, but also increase the range and complexity of molecules we are able to produce.

The stepwise building method used in IPISC means that amino acids with particular properties, such as increased stability, can to added at the beginning of the process. This method also used target proteins as the scaffold on which to built, ensuring the the synthesised protein can bind effectively with its intended target. IPISC is also relatively easy to scale up from screening to full production when a suitable protein is identified.

This review doesn’t just cover the advantages of IPISC, but also discusses effective ways to analyse the results of a screen and areas where the method could be optimised further. To find out more, download the review here – it’s free for the next four weeks.

In situ click chemistry: from small molecule discovery to synthetic antibodies
Steven W. Millward, Heather D. Agnew, Bert Lai, Su Seong Lee, Jaehong Lim, Arundhati Nag, Suresh Pitram, Rosemary Rohde and James R. Heath
DOI: 10.1039/C2IB20110K

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)