Archive for the ‘Chemistry World Highlights’ Category

Bacterial identification gets a culture shock

Scientists in the UK have developed a new tool to distinguish bacterial strains from each other. This speedy method could help to minimise drug resistance by accurately directing antibiotic treatment at an early stage.

Antimicrobial resistance is a major health concern and its risk is growing evermore due to a lack of both new drugs and rapid point-of-care diagnostic tools to ensure best use of the drugs in hand. ‘Innovative solutions to identifying pathogens can be found – which is really needed as antibiotic resistance spreads – if different fields work together,’ explains Matthew Gibson from the University of Warwick, whose group developed the new diagnostic tool.

Current point-of-care methods to identify bacteria require culturing bacteria to grow them to higher density – a very slow process. New sequencing technologies are faster, but still require hours and special equipment. Gibson’s method makes use of adhesion between bacteria and other cells. Many bacteria bind to cells through protein or carbohydrate structures exposed on the surface of the bacterium called adhesins. Each bacterial strain has a very specific pattern of adhesins and therefore binds with different strength to different sugar-bearing cell surfaces.


Read the full story in Chemistry World


Read the original journal article in Molecular BioSystems – it is open access.

Discrimination between bacterial species by ratiometric analysis of their carbohydrate binding profile
L. Otten, E. Fullam and M. I. Gibson, Mol. Biosyst., 2016, Advance Article
DOI: 10.1039/C5MB00720H, Communication

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Prostate cancer detection comes of phage

Researchers in the US have wrapped bacteriophage with the polymer PEG (polyethylene glycol) to make a structure that detects PSMA, a molecular flag for prostate cancer. Their system could save lives by spotting aggressive forms of the disease at an earlier stage.

 Engineering chemically modified viruses for prostate cancer cell recognitionBacteriophage are harmless to humans, and their surfaces can be easily modified to grab onto cancer biomarkers, which can be indirectly quantified by measuring the levels of enzymes attached to these biomarkers with an ELISA (enzyme-linked immunosorbent assay). However, non-specific adhesion between cell surface receptors and phage can lead to a reduced signal-to-noise ratio and therefore make it difficult to distinguish cancer cells.

Greg Weiss and Kritika Mohan at the University of California have overcome this issue by wrapping PEG around the phage M13. This creates a hydration sphere around the phage and limits non-specific cell adhesion, allowing them to distinguish PSMA-positive from PSMA-negative cells.


Read the full story in Chemistry World»


Read the original journal article in Molecular BioSystems – it is free to access until 30 November 2015.

Engineering chemically modified viruses for prostate cancer cell recognition
K Mohan and G Weiss, Mol. Biosyst., 2015, Advance Article
DOI: 10.1039/
C5MB00511F, Paper

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Smorgasbord of chemical blueprints located in plain pond algae

Euglena-gracilis

The pond algae Euglena gracilis has a surprising wealth of metabolic pathways for unexpected natural products, new research shows. Genes from this common single-celled organism could therefore be manipulated to synthesise a host of unusual, and potentially useful, compounds.

Euglenoids are a group of algae that grow abundantly in nutrient-rich freshwater environments, such as garden ponds. Euglena gracilis is known to produce many nutritional compounds including vitamins A, C and E, essential amino acids and polyunsaturated fatty acids. However, sequencing its genome in a bid to unlock these valuable natural products has proved very challenging due to its large size, complexity and incorporation of the unusual nucleotide base J.

Researchers, led by Rob Field at the John Innes Centre in the UK, have tackled this problem by instead looking at Euglena’s transcriptome – the mRNA transcribed from the genome that shows what genes an organism is using at a given time.



Read the full story in Chemistry World

Read the original journal article in Molecular BioSystems –  it is free to access until 15 October 2015

The transcriptome of Euglena gracilis reveals unexpected metabolic capabilities for carbohydrate and natural product biochemistry

Ellis C. O’Neill, Martin Trick, Lionel Hill, Martin Rejzek, Renata G. Dusi, Chris J. Hamilton, Paul V. Zimba, Bernard Henrissat and Robert A. Field.
Mol. BioSyst., 2015, Advance Article
DOI: 10.1039/C5MB00319A, Paper
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Drawing order from disorder to unravel Ebola’s lethality

The virulence of Ebola virus strains appears to be innately linked to the degree of disorder in proteins that form their nucleocapsids. Computational analysis has revealed that strains responsible for the most lethal outbreaks of Ebola show significantly higher levels of intrinsic protein disorder than less virulent strains, in a discovery that could constitute a major breakthrough in understanding the pathogen’s behaviour.

With over 27,000 confirmed, probable and suspected cases and more than 11,000 fatalities worldwide, the ongoing Ebola outbreak has resulted in considerably more casualties since late 2013 than all other outbreaks combined. There are no effective treatments or vaccines against the haemorrhagic fever that evinces Ebola infection; however, strains of the virus with drastically different virulence have emerged since the first outbreak in 1976, with fatality rates ranging from 25 to 90%.

In an effort to explain such radical variations in lethality, researchers Gerard Goh, from Goh’s BioComputing in Singapore, Keith Dunker, from the Indiana University School of Medicine in the US, and Vladimir Uversky, from the University of South Florida in the US, have computationally explored links between the virulence of different Ebola virus strains and their predicted protein structures. The group discovered that intrinsically disordered proteins (IDPs) encapsidating the virus’ genetic material appear to play a large role, with increasing levels of disorder correlating with greater virulence.


Read the full story in Chemistry World»

Read the original journal article in Molecular BioSystems – it is free to access until 24 July 2015.

Detection of links between Ebola nucleocapsid and virulence using disorder analysis
Gerard Kian-Meng Goh, Keith Dunker and Vladimir N. Uversky
Mol. BioSyst., 2015, Accepted Manuscript
DOI: 10.1039/C5MB00240K, Paper

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Schizophrenia: a disease of the brain?

Brain with question mark superimposed

The brain is usually considered as the most relevant organ of schizophrenia, but evidence suggests that peripheral tissues also contribute to the disease

Scientists in China have unearthed further evidence that a malfunction of the immune system contributes to the development of schizophrenia.

Schizophrenia is a severe mental illness, which affects around 1% of the world’s population. It is traditionally thought to be exclusively caused by problems in the brain. However, there is a growing body of evidence that suggests that the immune system has an important role to play.

Lin He and Chunling Wan from Shanghai Jiao Tong University, and their colleagues, identified over 1300 proteins in the blood and then compared the blood of schizophrenic patients with healthy blood using mass spectrometry. They found that 27 proteins were different in the schizophrenic patients and that all of these proteins were involved in the complement system.

See the full article in Chemistry World

Or read the Molecular BioSystems paper:

Label-free quantitative proteomic analysis reveals dysfunction of complement pathway in peripheral blood of schizophrenia patients: Evidence for the immune hypothesis of schizophrenia
Yang Li, Kejun Zhou, Liya Sun, Jinglei Yang, Ming Zhang, Baohu Ji, Kefu Tang, Zhiyun Wei, Guang He, Linghan Gao, Lun Yang, Peng Wang, Ping Yang, Guoying Feng, Lin He and Chunling Wan
Mol. Biosyst., 2012, DOI: 10.1039/C2MB25158B

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Fishing for chemical answers to biological questions

James K. Chen is an associate professor in the Department of Chemical and Systems Biology, Stanford University School of Medicine, US. He uses chemical tools to study developmental biology, including caged oligonucleotides that can regulate embryonic gene expression in zebrafish and other model organisms.

When did you decide to go into chemical biology?

It was when I was an undergraduate, during a lecture given by Stuart Schreiber at Harvard University. He was talking about his work on the immunosuppressive compound FK-506. His laboratory had found that FK-506, and another molecule called cyclosporin, inhibited the activity of calcineurin, a serine/threonine protein phosphatase. These studies were important because they implicated a role for calcineurin in T cell function and provided new insights into how T cell receptor signalling is transduced from the cell surface to the nucleus. After that lecture, I immediately knew that this was the kind of research I wanted to do. I loved organic chemistry, but I was more interested in answering the questions of biology. Using a small molecule to gain insight into a complex biological process was exactly what I wanted to do.

What can chemistry bring to developmental biology?

Chemistry can bring an understanding of biological mechanisms at the molecular level. It enables us to learn what is biologically interesting with molecular clarity. At the technology level, chemistry can help us to break through the natural system, for instance, chemists can make a molecule that doesn’t exist in nature and see the effect it has on a biological system. Chemical technology can break the bounds of biology.

What advice would you give to a chemist who is considering moving into biology?

A key difference between the two disciplines is the degree and level of focus – chemists tend to focus on techniques and they want to understand a system in terms of the simplest model possible; it’s a reductionist approach. With biology, you almost need peripheral vision – the system you’re trying to understand is like a forest, with complexity at many different levels and you have to be aware of it all. Often the simplest answer is not the correct one. Also, there’s a lot to learn, but it’s like learning a new language – if you immerse yourself in it, in time, you can know as much about your particular field as your biology colleagues do.

If you weren’t in this field, where would you have ended up?

I think I would have still been a developmental biologist, but any area of developmental biology is interesting to me. My interest isn’t focused on one particular organism; rather, it’s all about answering the key question: how does pattern form from nothing? It’s about basic architecture. Of course, developmental biology is also related to cancer biology, since many embryonic signalling pathways are dysregulated in tumours, but primarily my interest is fundamental rather than applied.

When you’re not doing science, what do you enjoy doing?

One thing I like to do is run; I normally do a half marathon every three months or so. Also I love fly fishing – it’s my passion. Once a year, I meet up with some old friends from our grad school days and we go fly fishing together. It’s a great way to catch up and enjoy nature at the same time. I love the outdoors so I enjoy anything that gets me out of the office into the natural world.

To read the full interview see Chemistry World and for some of James Chen’s recent research see:

Gene regulation technologies in zebrafish
Hanife Esengil and James K. Chen
Mol. BioSyst., 2008, 4, 300
DOI: 10.1039/b718447f

Chemical technologies for probing embryonic development
Ilya A. Shestopalov and James K. Chen
Chem. Soc. Rev., 2008, 37, 1294
DOI: 10.1039/b703023c

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Identifying the cause of pregnancy loss

Western blot analysis of ITI-H4 in RPL and normal patients. The fragmented ITI-H4 (36 kDa) was detected in 19 out of 29 RPL patients

A protein has been identified as a possible indicator of recurring pregnancy loss by scientists from Korea.

Kwang-Hyun Baek from CHA University, Seoul, and colleagues found that ITI-H4, a protein found in the blood whose function is unclear, was fragmented in the blood samples of patients suffering from recurrent pregnancy loss (RPL).

‘RPL is the loss of at least three consecutive pregnancies after 20-28 weeks,’ explains Baek who adds that over half of the possible causes are unknown. ‘We have seen a number of patients suffering from RPL without knowing the cause,’ he says.

Baek hopes to develop a diagnostic kit to screen RPL patients. ‘In the long term, we would like to develop a therapeutic approach to suppress the risk of RPL,’ he adds. ‘We’re not sure whether the fragmentation of the protein ITI-H4 is the result or cause of RPL so identification of its cellular mechanism is required to develop therapies.’

Read the full Chemistry World story online here or the full article at:

ITI-H4, as a biomarker in the serum of recurrent pregnancy loss (RPL) patients
Myung-Sun Kim, Bon-Hee Gu, Sangjin Song, Bum-Chae Choi, Dong-Hyun Cha and Kwang-Hyun Baek
Mol. BioSyst., 2011, Advance Article
DOI: 10.1039/C0MB00219D

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Diet affects cholesterol drug

Copper and zinc in the diet could impair the action of statin drugs, compounds prescribed to lower cholesterol, say US scientists.

What started as a summer project in a lab at the University of Washington in Seattle led to an unexpected find. Douglas Fowler from Stanley Fields’ group came up with a project to study the effect of combining drugs with 52 metabolites on yeast cell growth. ‘At the end of the summer, we hadn’t gathered much useful data, but I was convinced that the idea was a good one,’ says Fowler. ‘We continued with the experiments and found an unexpected result – copper and zinc impaired statin effectiveness.’ 

Statins work by inhibiting an enzyme that’s responsible for cholesterol synthesis and are used to prevent heart disease. It’s known that metabolites – molecules that break down food to provide energy in a process called metabolism – in the body can interact with drugs, but understanding how these interactions happen could enhance drug performance and reduce side effects.

The team found that with lovastatin present, the metal ions had increased the level of proteins responsible for making ergosterol, a cholesterol analogue responsible for growth in yeast. They went on to test this in cultured mammalian cells too and got the same result with cholesterol.



Copper and zinc increased levels of ergosterol and related intermediates in the presence of lovastatin

Link to journal articleSuppression of statin effectiveness by copper and zinc in yeast and human cells
Douglas M. Fowler, Sara J. Cooper, Jason J. Stephany, Natalie Hendon, Sven Nelson and Stanley Fields,
Mol. BioSyst., 2011, 7, 533, DOI: 10.1039/c0mb00166j

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Early lung cancer diagnosis

Patients with lung cancer have elevated levels of a specific protein in their blood that could be used as a biomarker for the disease, say scientists from South Korea.

Je-Yoel Cho from Kyungpook National University and colleagues saw that levels of the beta chain form of haptoglobin – a protein produced by the liver when disease is present – increased in blood samples when lung cancer cells were present.

Among cancer types, lung cancer frequently ranks at the top in both incidence and mortality, according to the World Health Organisation. The discovery of novel lung cancer specific biomarkers – substances in the blood whose levels indicate the presence and extent of the disease -is important for early detection. Current techniques to detect cancer aren’t able to give an early diagnosis.
Read more on this story

Link to journal article
The Haptoglobin chain as a supportive biomarker for human lung cancers
Sung-Min Kang, Hye-Jin Sung, Jung-Mo Ahn, Jae-Yong Park, Soo-Youn Lee, Choon-Sik Park and Je-Yoel Cho
Mol. BioSyst., 2011, DOI: 10.1039/c0mb00242a

High levels of the beta chain form of haptoglobin - a protein produced when disease is present - could be an indicator of lung cancer. (C) Nature

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DNA vaccine induced autoimmune disease

Safety concerns over the use of a DNA vaccine have been raised by Chinese scientists after they observed that it induced autoimmune disease in mice.

DNA vaccines are genetically engineered parts of virus DNA that are injected into the body to boost the immune system’s response to viral, bacterial and parasitic pathogens. Cells in the body convert the DNA into proteins that are recognised as foreign by the immune system, which triggers a response. In conventional vaccines, weakened or killed forms of the virus are injected. DNA vaccines eliminate the risk of infection associated with conventional vaccines, are extremely stable and can provide long-lived immune responses.

However, Shuhan Sun and his team from the Second Military Medical University, Shanghai, were testing mice for reactions to a DNA vaccine called pcDNA3-b1. They noticed that the mice developed symptoms of vitiligo – a skin pigmentation disorder where patches of skin lose colour – within six weeks of a third immunisation.

Mice developed vitiligo symptoms within six weeks of a third immunisation

Click here to read the full story

Link to journal article
Down-regulation of Prdx6 contributes to DNA vaccine induced vitiligo in mice
Qi Zhou, Fang Wang, Yi Zhang, Fu Yang, Yue Wang and Shuhan Sun, Mol. BioSyst., 2011
DOI: 10.1039/c0mb00181c

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