Archive for the ‘Reviews’ Category

HOT Review! Understanding complexities of the brain with genomics and proteomics

This HOT review is all about the advances in sequencing, proteomics and bioinformatics and how they are shaping our knowledge of neural molecular complexities.

This fascinating HOT review from Beena Kadakkuzha and Sathyanarayanan Puthanveettil at The Scripps Research Institute, USA, delves into the tools we can use to understand neural proteomics and genomics, why this is useful and how we can pull the information together to explain observations of higher brain function. They include: 

  1. Relationship between gene expression and brain function
  2. The need for functional genomics and proteomics
  3. Sequencing, microarrays and next generation sequencing
  4. Genomic databases
  5. Single cell analysis
  6. High-throughput challenges

This truly interesting review is now free to access for four weeks*, so you can read it now:

Genomics and proteomics in solving brain complexity
Beena M. Kadakkuzha and Sathyanarayanan V. Puthanveettil
DOI: 10.1039/C3MB25391K

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HOT review: The paradigm shift in target protein identification methods

This HOT review article from MBS Associate Editor Seung Bum Park and colleagues at Seoul National University, Korea, reviews the changing methods used for target protein identification.

This review covers:

  1. Limitations of affinity-based methods
  2. The shift to using chemoreactive groups
  3. Use of photoreactive groups for wider applications
  4. Increased specificity of Fluorescence difference in 2D Gel Electrophoresis (FITGE)

They conclude that each approach has its advantages for different applications and no one method is dominant. However, there has been an obvious move from non-covalent to covalent-based methods, with increasing specificity and general applicability leading to higher success rates.

Read the detailed review of the pros and cons of current methods and where the latest technology may take us in this HOT review, which is free to access for the next 4 weeks*:

From noncovalent to covalent bonds: a paradigm shift in target protein identification
Jongmin Park,  Minseob Koh and Seung Bum Park
DOI: 10.1039/C2MB25502B

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

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Hot Review: Directed evolution for synthetic genetic circuits

Directed evolution is a method normally used for protein engineering, but in this HOT review, Yolanda Schaerli and Mark Isalan at Universitat Pompeu Fabra, Barcelona, Spain, highlight the ways in which it can be used to design novel gene networks.

The challenges of synthetic biology mainly revolve around the fact that our knowledge of complex natural biological systems is incomplete. Therefore, creating biological networks is often a tedious trial-and-error process. Using the principles of directed evolution can be a tool to bridge the gaps. In protein engineering, this means from a large library of diverse individuals only those with the desired properties survive the rounds of screening and selection; the same principle is now being applied to biological circuits.

This review includes:

–          Choice of library size and where to introduce diversity in the network in regulatory components such as promoters and ribosomal binding sites, or protein components

–          Screening for desired variants using fluorescence and flow cytometry

–          Selection methods, including tailoring the selection to the application and careful analysis of the results.

Concluding remarks are centred around the emerging technologies which will enable more practical options for screening of genetic circuit libraries and cellular networks where each cell carries out a simple task contributing to the complex function of the group.

Building synthetic gene circuits from combinatorial libraries: screening and selection strategies
Yolanda Schaerli and Mark Isalan
DOI: 10.1039/C2MB25483B

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

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Review – Protein labelling with synthetic fluorescent probes in live cells

fluorescent probesThis article by Youngeun Kwon et al, at Dongguk University and Korea Research Institute of Bioscience and Biotechnology, Korea, reviews the chemical biology approach of fluorescent labelling to study protein interactions in live cells in real time.

This review addresses the diverse array of chemical biology methods for incorporating synthetic probes to proteins of interest, including:

  1. Use and limitations of fluorescent proteins
  2. Chemical recognition-based labelling and metal–ligand interactions
  3. Highly specific biological recognition-based labelling using proteins and enzyme–substrate interactions
  4. Multifunctional probe development

The group discuss the limitations and advantages of the many techniques, using specific examples and detail. There are many parameters to consider during the optimisation of fluorescent labelling methods and the chosen method needs to meet the needs of the specific experiment. Much current work is focused on improving the ability to monitor the activity of proteins in live cells, requiring greater control over the labelling, for which the available techniques are inadequate.

This review is now free to access for the next 4 weeks*, just click on the link below:

Chemical biology-based approaches on fluorescent labeling of proteins in live cells
Deokho Jung, Kyoungmi Min, Juyeon Jung, Wonhee Jang and Youngeun Kwon
DOI: 10.1039/C2MB25422K

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

 

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A review – Utilising the data-rich omics knowledge base

The influx of data from omics studies is ever increasing due to recent technological advances enabling large-scale measurement of the simultaneously acting molecular components such as proteins, nucleic acids and metabolites. Using this wealth of information for meaningful analysis has turned out to be a challenging task.

Such data can be analysed in different ways, but this review article from Daniel Hyduke et al. at University of California, (San Diego) and Harvard Medical School, USA, concentrates on the use of the established omics knowledge base to reconstruct biological networks. Such reconstructions can then be used as mathematical models to be tested. The review focuses on genome-scale models of metabolism and includes: 

  1. Comparing omics data with predictions or simulations
  2. Using omics to elucidate the rules of regulation for environment-specific models
  3. Perspective on current limitations and challenges

The authors conclude that this kind of analysis is still in its infancy, with greater consistency between network models and omics data needed – which will come from a more complete data set and advances in modelling as research steadily continues. However it is still currently an extremely useful method of gaining further insight into biological systems.

The full fascinating review is free to access for the next 4 weeks*, read it here by clicking the link below:

Analysis of omics data with genome-scale models of metabolism
Daniel R. Hyduke, Nathan E. Lewis and Bernhard Ø. Palsson
DOI: 10.1039/C2MB25453K

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

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A review – it takes two to tango if you’re a Raf kinase

Researchers at University College Dublin, Anglela Baljuls, Boris Kholodenko and Walter Kolch, look at the role of dimerization of Raf kinases in the MEK-ERK pathway in cancer and the implications for design of drug therapies in this recent review.

Raf tango signallingThe MEK-ERK pathway is involved in the effect that extracellular stimuli have on processes happening inside the cell, such as proliferation and apoptosis to name just two. Mutations of the proteins in this pathway can result in them being stuck in the inactive or active form, giving rise in many cases to different forms of cancer. Raf is a group of proteins central to this signalling pathway. The regulation of active and inactive forms of Raf is complicated, but Raf dimerization is known to play a part. This in-depth review examines:

1. Inducing and inhibiting Raf dimerisation

2. Why dimerization is necessary

3. How does dimerization affect cell proliferation and tumour formation?

4. Targeting Raf and drug inhibitor design

As pointed out in the review, Raf has made the headlines as an important piece of the puzzle with regard to cancer treatment, but this review shows that research on Raf regulation is ongoing with dimerization playing a critical role.

Read the full review here:

It takes two to tango – signalling by dimeric Raf kinases
Angela Baljuls, Boris N. Kholodenko and Walter Kolch
DOI: 10.1039/C2MB25393C

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EGFR activation dynamics, inhibiting MRSA and transcription factor diffusion

Don’t know what to do with your Friday afternoon? Why not take a look at our latest HOT article! We make all our HOT articles free to access for 4 weeks:

Integrated experimental and model-based analysis reveals the spatial aspects of EGFR activation dynamics
Harish Shankaran,  Yi Zhang,  William B. Chrisler,  Jonathan A. Ewald,  H. Steven Wiley and Haluk Resat
DOI: 10.1039/C2MB25190F

Or if that’s not in your field, we’ve also just published two new review articles:

Computational models for large-scale simulations of facilitated diffusion
Nicolae Radu Zabet and Boris Adryan
DOI: 10.1039/C2MB25201E

Inhibitors targeting on cell wall biosynthesis pathway of MRSA
Haihong Hao,  Guyue Cheng,  Menghong Dai,  Qinghua Wu and Zonghui Yuan
DOI: 10.1039/C2MB25188D

Access to free content is provided to individuals through a free RSC Personal Publishing Account.

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Genetic Tug-Of-War and cell robustness – a review

In this review, Hisao Moriya and co-authors explore the analysis of robustness in cellular systems, focusing on their experimental approach ‘genetic Tug-Of-War‘ (gTOW).

The article compares the gTOW method with mathematical simulation models that are currently used to determine robustness, and goes on to fully describe the experimental principles underlying gTOW and its associated tools. Various examples of robustness analysis using gTOW are given, including cell cycle and HOG pathway gene expression analysis.

The following questions are some of those answered by the review:

  • Does DNA itself determine the plasmid copy number in gTOW analysis?
  • Does the amount of protein correlate with the gene copy number?
  • Does reversion occur during the experiment?
  • Is “100-fold increase in gene copy number” an impossible perturbation for the cellular system?

Find the all the answers and further information in the full article:

Robustness analysis of cellular systems using the genetic tug-of-war method
Hisao Moriya, Koji Makanae, Kenji Watanabe, Ayako Chino and Yuki Shimizu-Yoshida
DOI: 10.1039/C2MB25100K

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Reviewing techniques to understand the role of oxidative stress in psychiatric disorders

In this review Ana Cristina Andreazza looks at the use of redox-proteomics and epigenomics to improve our understanding of the pathophysiology of psychiatric illnesses such as biopolar disorder and schizophrenia.  Oxidative stress and mitochondrial dysfunction have recently been implicated as common features in major psychiatric disorders, but only through a combination of techniques can we begin to understand the nature of oxidative modification, its potential to change protein–protein interactions and induce epigenetic modification says Andreazza.  Understanding the molecular targets for oxidation should hopefully lead to the development of new drug treatments or disease biomarkers.

The review covers:
1. Oxidative stress and redox balance
2. The link between DNA oxidation and DNA methylation
3. Psychiatry and oxidative stress: what do we know so far?
4. Developing biomarkers to assist in predicting the course of psychiatric illnesses

Combining redox-proteomics and epigenomics to explain the involvement of oxidative stress in psychiatric disorders
Ana Cristina Andreazza
DOI: 10.1039/C2MB25118C

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Transforming the hydroxyl group

The hydroxyl group is a tricky moiety to convert to another functional group, as it is less reactive than other common groups such as amines, thiols or carboxylic acids and reactions are often thwarted by the presence of water.  It is, however, present in many biologically significant molecules – ~65% of known natural products, ~40% of drugs, several classes of lipids and three of the 20 common amino acids according to this review by Darci J. Trader and Erin E. Carlson.   They look at the currently available methods to transform this important group, with particular emphasis on methods that are useful for chemical biology applications.

Areas covered include:

  • Direct conjugation reactions
  • Activation by generation of a leaving groupHydroxyl group transformations for chemical biology
  • Alcohol oxidation
  • Transformation to an alternative chemical handle
  • Natural product analog for target identification
  • Functional group-mediated enrichment of alcohols
  • Chemoselective protein bioconjugation
  • Hydroxyl groups in enzyme active sites

Chemoselective hydroxyl group transformation: an elusive target
Darci J. Trader and Erin E. Carlson
DOI: 10.1039/C2MB25122A

This paper is free to access for 4 weeks following a simple registration for individual users.

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