Category: Micro-biology

Researchers University of California, San Diego School of Medicine, along with colleagues in The Netherlands and United Kingdom, have constructed a map detailing the genetic reactions underlying the response of cells to ultraviolet radiation (UV) exposure.

It is hoped the study will shed light on the ways in which cells are damaged by radiation and on the mechanisms that repair cells. UV radiation can cause malignancy, especially in skin cancers, and understanding the repair mechanisms may enable scientists to gain more insight into the process of cancer formation.

Some 89 UV-induced functional interactions were studied among 62 protein complexes. These interactions were taken from a larger measurement involving the deletion of two separate genes. Observations were made before and after different doses of UV radiation.

Links were identified between the radiation and the cell's chromatic structure remodelling complex (RSC). Chromatin is a combination of DNA and proteins which forms a cell's nucleus and is remodeled during cell division. According to the researchers, RSC is directed to places on damaged genes and DNA, helping to facilitate effective repair.

The nucleotide excision repair (NER) pathway identifies DNA-distorting lesions and removes them from the genetic material. The gap is then filled with new genetic material copied from an undamaged DNA strand and sealed by an enzyme.

NER works in conjunction with other mechanisms, including RSC.

Dr Rohith Srivas explained that in order to do their job, repair factors need access to undamaged DNA. Chromatin remodelers can be recruited to the DNA and open it up for the repair factors to perform their function.

"Our results are novel because they show RSC is connected to both UV damage pathways: transcription coupled repair – which acts on parts of DNA being expressed – and global genome repair, which acts everywhere. All previous remodelers were linked only to global genome repair," Dr Srivas commented.

The scientists observed that the degree of genetic rewiring is correlated with the dose of UV. Reparative interactions were observed at distinct high or low doses of UV.

Researchers at Emory and Georgia Tech have discovered a new technique which combats atherosclerosis by targeting a micro-RNA molecule instrumental to its development.

It was discovered that a drug that blocks micro-RNA – a molecule left over from ribosome formation – slows down the process of atherosclerosis. In animal models, the process was blocked despite the presence of a high fat diet.

While it is well known that exercise reduces the likelihood of atherosclerosis, the latest research helps to explain why this is the case.

Atherosclerosis occurs when the walls lining the arteries thicken due to a build-up of white blood cells, lipids and cholesterol; this can bring on strokes and heart attacks. A constant flow of blood through the arteries prevents atherosclerosis, whereas an erratic flow of blood is known to contribute to the disease's development. 

The scientists developed an animal model of the disease, inducing atherosclerosis in mice by partially restricting the blood flow in the carotid artery. The mice were fed a high-fat diet and bred to have a deficiency of Apoe, which removes lipids from the blood.

As part of the research, the team focussed on micro-RNAs, which can inhibit several genes at one. It has recently been discovered that these can travel between cells and therefore have the potential to cause atherosclerosis. One micro-RNA, miR-712, was found to be induced by an erratic blood flow.

Cells produce miR-712 in response to an erratic blood flow, which inhibits a gene that reduces inflammation in endothelial cells, which line blood vessels, in normal conditions. The team found that miR-712 is leftover from ribosomes, which produce protein molecules.

A technology called 'locked nucleic acids' was used to block miR-712 in the body. It was discovered that this helped prevent the mice from developing atherosclerosis. The drug reduced by 50 per cent the portion of the carotid artery blocked by plaques.

The team is currently conducting research using nanotechnologies to deliver ant-miR-712 drugs directly to the heart and endothelial cells in a technique that will keep side effects to a minimum.

Researchers in Singapore believe they could develop a new malaria vaccine within the next five years.

The team at Nanyang Technological University (NTU) have come across a new process which occurs when the malaria parasite attempts to invade the body.

They have honed antibodies that can prevent the disease from infecting red blood cells.

Professor Peter Preiser, chair of NTU's School of Biological Sciences, explained how this works in simple terms.

"What we have identified is a region of the malaria parasite which it uses to attach to a healthy blood cell then pushes itself into the cell," he commented.

"So imagine the parasite has the key to unlock a door to the red blood cell, but we muck the key up, so no matter how hard the parasite tries, the door just refuses to open."

The researchers have spent five years on these latest tests and the results could pave the way for a number of advanced treatments in the future.

Mr Preiser believes that if the NTU team can join forces with a drug development company, a potentially landmark new vaccine could be created before the end of the decade.

The NTU has an impressive record of turning breakthrough discoveries such as this into fully-fledged treatments.

Researchers will now use this new technique to find other antibodies that can target the malaria parasite, which could lead to even more new treatments further down the line.

Figures provided by the World Health Organisation highlight the huge impact this new discovery might have around the world.

Some 627,000 people died from malaria in 2012 alone, with the majority of these being young Africans.

Overall, there were around 207 million cases of the disease across the globe last year.

Although mortality rates have fallen significantly – by 45 per cent internationally since 2000 and by 49 per cent in Africa – doctors and scientists are keen for new, cheap vaccines to be brought to market as soon as possible.

Research into Alzheimer's has previously focussed on whether amyloid-beta or tau proteins are the symptoms or cause of the disease.

A new study at the University of Virginia, however, suggests that earlier interactions between the two proteins cause the disease by encouraging mature neurons to undertake "cell cycle re-entry" – a process they should not normally undergo.

According to leader of the study Dr George Bloom, amyloid-beta oligomers disrupt a critical balance point between tau and a master cellular regulator, which leads to the onset of the disease.

Mature cells which have finished dividing are 'post-mitotic' and thus locked outside of the cell cycle. In patients with Alzheimer's disease (AD), however, neurons frequently re-enter the process of cell division, fail to complete it fully and die.

In the final stages of the disease, up to 30 per cent of the cells that make up the brain's frontal lobes are dead; they are surrounded by amyloid plaques and tau-associated neurofibrillary tangles.

"The massive neuron death that occurs in AD therefore appears to be caused by the raw ingredients of plaques and tangles working in concert with each other, rather than by the plaques and tangles themselves," Dr. Bloom explained.

The new discovery follows on from earlier research in which amyloid-beta was found to activate protein kinases to add phosphates to sites on tau, leading neurons to begin the process of cell cycle re-entry.

Follow-up research by Dr Bloom's team demonstrates that a novel group of proteins – Rac1, Gαs (Gs alpha), and NCAM – and two protein kinases complexes – mTORC1 and mTORC2 – are required to disrupt cell cycle re-entry.

The delicate balance of regulation that normally occurs between tau and mTOR is upset by amyloid-beta oligomers. When the balance is upset, cells re-enter the cycle, fail to divide and die.

"Some of the earliest events in AD pathogenesis are therefore caused by amyloid-beta oligomers altering a fundamental neuronal signaling axis centered around tau and mTOR," said Dr Bloom.

New research has shed light on the ability of cells to form "bridges" which facilitate the wound healing process.

Researchers at the National University of Singapore (NUS) made the discovery, which stands to benefit several areas of tissue engineering, including wound treatment and artificial skin.

The team were able to identify the process by which skin cells migrate over areas that do not possess the extracellular proteins to which cells adhere. The findings were published online in the journal Nature Materials.

Microfabricated technology was used to discover how outer skin cells, known as keratinocytes, are able to migrate en masse over regions that lack the extracellular proteins. These cells are able to coalesce and form suspended bridges over the damaged section of skin.

During their study the researchers discovered that a motor-protein known as acto-myosin played a key role in enabling the cells to form bridges. The motor-protein causes a buildup of tension, as it encourages cells to contract. The consequent elastic-like behaviour of the cells facilitates bridge formation.

The process by which cells are able to form a barrier over an area that does not possess the structural proteins was not previously understood.

Commenting on the research, one of the leaders of the study professor Lim Chwee Teck said that an in-depth knowledge of the factors playing a role in tissue repair is necessary. "Our study will hopefully pave the way for designing better alternatives that can overcome the current limitations in the field of skin tissue engineering and promote satisfactory skin regeneration. Some potential applications include treating skin burn wounds as well as characterising the mechanical properties of cell sheets," he commented.

The team hope to build on their research by investigating the physical and mechanical properties of skin cells. It is hoped this will provide an insight into many of the skin conditions associated with blistering and others which occur as part of the ageing process. 

A study conducted by the Scripps Research Institute in Florida has identified a treatment that could improve the symptoms of rheumatoid arthritis, a disease which affects nearly 300,000 Britons.

Rheumatoid arthritis is an autoimmune condition that causes swelling of the joints and leads to restricted movement in sufferers, commonly occurring during middle age. The new research uses a compound which acts directly on cells, significantly reducing joint inflammation. It could see more effective treatments created for the disease.

A compound known as SR2211 was found to alleviate symptoms in mice with rheumatoid arthritis. Indeed, within eight days of treatment, virtually all symptoms of the disease had been blocked. The mice also showed diminished bone and cartilage erosion compared to a group of healthy mice.

The compound targets the nuclear RORy receptors, which are instrumental in regulating TH17 white blood cells thought to play a role in the development of a number of conditions such as multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease.

The team found the compound blocked the release of inflammatory mediators from TH17 cells in culture, and they are confident it will have a similar effect in rodents.

Although treatments are available for arthritiscomma these tend to be long-term immunosuppressants which leave patients vulnerable to a range of other infections. Their use is associated with increased infection rates and the contraction of conditions such as pneumonia. This problem would be avoided with an orally-administered treatment that could be taken daily.

"This compound, and its precursors, showed the ability to block the release of specific inflammatory mediators from TH17 cells in culture, so we were confident that SR2211 would demonstrate good efficacy in rodent models of autoimmune disease," said biochemist Patrick Griffin, chair of the TSRI Department of Molecular Therapeutics. "Our newest study strongly supports the idea that by targeting the RORγ receptor, we can therapeutically repress inflammation and joint destruction associated with rheumatoid arthritis."

The new compound stands to benefit patients who cannot tolerate conventional treatment, offering doctors new options.

A new stem cell treatment being developed at Loyola University could offer hope to patients suffering from leukaemia, lymphoma and other blood cancers. 

The technique uses stem cells derived from umbilical cords, which are grown in a laboratory before being transplanted into patients.

According to Patrick Stiff, lead author of the study, the new treatment could boost the survival rate of patients undergoing transplants from umbilical cords. He presented his findings at the 2013 annual meeting of the American Society of Hematology.

Patients who undergo chemotherapy and radiotherapy as treatment for cancer have healthy blood cells damaged by the treatments that are used to kill the cancerous cells. Stem cells are used to replace these cells in affected patients, as they have the capacity to develop into healthy new cells.

Stem cells are formed in the bone marrow. Previously, patients have had to rely on donations from relatives or people on the bone marrow registry – but these do not always provide a perfect match, with more than half of sufferers unable to find a matching donor. 

The new technique overcomes these difficulties, however, as stem cells derived from an umbilical cord blood bank do not require a perfect match.

A further problem with cord blood transplants is that many patients need to have a double dose of stem cells, as they contain only a small quantity of blood.

The study used a new form of technology to grow stem cells in a laboratory, increasing the number available for transplant. After 21 days, the number of stem cells had grown 14 times.

An experiment was conducted in which the new technology was used for cord blood transplants. Patients treated with the new method were found to have a significantly higher survival rate than those in a historical control group – 84.2 per cent compared with 74.6 per cent. Cells administered using the new method were also found to be more likely to engraft – to develop into new cells – compared with the previous study.

Researchers at the University of Pennsylvania have successfully sent proteins across the blood-brain barrier to reduce the plaques associated with Alzheimer's disease.

The blood-brain barrier, which is a dense cluster of cells that only allows small molecules to pass through, plays a vital role in preventing infections from attacking the brain, but it also obstructs potential treatments for conditions such as Alzheimer's.

Led by professor Henry Daniell, the research team combined cholera toxin b (CTB), a receptor which targets neurons, with myelin basic protein (MBP), a molecule that breaks down the plaques believed to cause memory loss. The molecules were also able to cross the blood-retina barrier, enabling them to break down the plaques that form in the eyes of Alzheimer's sufferers.

In order to prove their initial hypothesis, the team fed a group of mice freeze-dried leaves which had been genetically engineered to express the fused proteins. A green-flourescent protein molecule was combined with the CTB carrier, allowing the team to ascertain whether the protein had reached the brain. The team were able to identify the molecule in the brains and the retinas of the mice.

"When we found the glowing protein in the brain and the retina we were quite thrilled," said Professor Daniell. "If the protein could cross the barrier in healthy mice, we thought it was likely that it could cross in Alzheimer's patients brains, because their barrier is somewhat impaired."

The research team exposed the brains of mice bred to have Alzheimer's disease to the CTB-MBP compound and administered a stain that binds to the brain plaques. Their results showed a reduction in staining, indicating that the plaques were dissolving. 

The same type of test was performed on brain tissue from patients who had died of Alzheimer's disease, resulting in a significant decrease in staining in the parietal cortex – a part of the brain associated with the development of the disease. 

Finally, capsules containing the CTB-MBP compound were given to mice that had been bred to develop Alzheimer's. A reduction in plaques was reported compared to a control group of mice that was fed a capsule containing lettuce leaves.

Professor Daniell hopes to expand his research to ascertain whether associated memory problems are reduced in mice after they ingest CTB-MBP.

Researchers at the University of Vermont have identified a new procedure involving stem cell therapy to treat patients suffering from heart disease.

The research, which was carried out by University of Vermont Associate professor of medicine Jeffrey Spees, and colleagues, uses a type of bone marrow-derived progenitor to improve cell engraftment.

Stem cells have the potential to develop into a wide variety of cell types within the human body and can be used to repair damaged tissue. Researchers have struggled with cell engraftment until now and have only had limited success in grafting cells from culture back to injured tissue.

These latest experiments used the type of bone-marrow progenitor that forms stromal cells, which form connective tissue and play a role in the creation of blood cells. Stromal cells produce ligands, which protect injured tissue and promote tissue repair. The ligands interact with receptors on the surface of stem cells, instructing them to adhere, divide, or differentiate into a mature cell.

Professor Spees and his colleagues isolated a medium taken from the human bone marrow-derived progenitor cells and discovered that it contained Connective Tissue Growth Factor (CTGF) and the hormone insulin. This enabled them to confirm that the ligands would protect a cardiac progenitor cell and facilitate engraftment.

An experiment was conducted in which a rodent with heart infarction was treated with 'naked' stem cells and with cells that had been incubated in a medium of CTGF and insulin on ice for approximately 30 minutes; the cells were grafted sub-epicardially. The results showed that the priming cocktail increased graft success.

“We broke the record for engraftment!” exclaimed Spees. His team continues to study cell grafts in rodents and could extend the technique to humans in the future.

Coronary heart disease remains the most common cause of death in the UK, accounting for 74,000 fatalities each year. Professor Spees' research stands to benefit the 2.3 million people who suffer from the disease in the UK; in particular, it could enable bypass patients to have their cells harvested at their first surgery and used to partially rebuild their heart if they return for further treatment.

British companies are being urged to support the UK's burgeoning synthetic biology industry.

The government wants firms to develop new tools and services that will help this increasingly important sector grow.

On a global scale, the market for synthetic biology technology is expected to be worth $10 billion (£6.17 billion) by 2016 and the British authorities are planning to increase their investment in this area.

Up to £3.8 million is being made available to organisations through a campaign supported by the Biotechnology and Biological Sciences Research Council (BBSRC), Technology Strategy Board, Welsh government and Physical Sciences Research Council.

Synthetic biology is the term given to the use of engineering tools and approaches to whole organisms, biological cells and biochemical pathways.

There are a multitude of potential benefits to be had from investing in this kind of scientific research, not least the development of more effective pharmaceuticals. It can also lead to increased agricultural production and the creation of renewable energy sources.

UK science minister David Willetts said: "As one of the eight great technologies, synthetic biology has the potential to create exciting products, such as new antibiotics, helping to boost growth and keeping the UK ahead in the global race.

"Establishing new tools and services for the development of synthetic biology will significantly increase the rate of commercialisation in this emerging sector."

Iain Gray, chief executive of the Technology Strategy Board, added that the development of new tools and processes will ensure British businesses are at the forefront of the international synthetic biology sector.

A number of projects are already ongoing, including a collaboration between the BBSRC-funded John Innes Centre and antibiotic discovery firm Demuris, which is aimed at enhancing the effectiveness of antibiotics used to tackle hospital-acquired infections.

Although figures published by the Office for National Statistics showed the number of people dying from MRSA infections continues to fall in the UK, the NHS is understandably keen to ensure patients receive maximum protection when they stay in hospitals, so these studies could prove to be vital.