Crick News

ISSUE 16

Science snippets

sci_snippet_503x430px.jpg

Fruit fly discovery provides insights into brain stem cell development   

New research by a team at the Medical Research Council's National Institute for Medical Research (NIMR) explores the mechanisms by which neural stem cells are generated and produce their offspring. Neural stem cells are a type of brain cell that continuously divides and produces new and different nerve cells, or neurons.
 
Animal brains are organised into different areas with distinct functions, each made up of many types of neurons. Scientists had shown that this diversity is caused by patterning of neural stem cells in different parts of the brain, but did not know whether other mechanisms also could contribute.
 
Published in Nature Neuroscience, the research by Holger Apitz and Iris Salecker has identified a new strategy for generating neurons in the brains of the fruit fly Drosophila.
 
In many parts of the fly brain, neurons are typically produced by cells called neuroblasts, the fly equivalents of neural stem cells. When these divide, each neuroblast produces one new copy of itself and one other cell that divides to generate neurons.
 
However, the scientists identified one region in the fly's visual system that uses a strategy involving the production of precursor cells that move from one region to another before developing into neural stem cells and giving rise to neurons. This strategy is remarkably similar to a process observed in the mammalian brain, and therefore may also occur in humans.

Future studies will be able to use this region of the Drosophila brain as a model to understand what happens in mammalian brains. In the long term, this could help to understand brain disorders caused by developmental defects.

 

Research suggests ability of HIV to cause AIDS is slowing

The rapid evolution of HIV, which has allowed the virus to develop resistance to patients' natural immunity, is at the same time slowing the virus's ability to cause AIDS, according to new research funded by the Wellcome Trust.

The study, published in the Proceedings of the National Academy of Sciences, also indicates that people infected by HIV are likely to progress to AIDS more slowly - in other words the virus becomes less 'virulent' - because of widespread access to antiretroviral therapy (ART).

Both of these factors make an important contribution to the overall goal of the control and eradication of the HIV epidemic. In 2013, there were a total of 35 million people living with HIV worldwide, according to the World Health Organization.

The research was carried out in Botswana and South Africa, two countries that have been worst affected by the HIV epidemic. Across those countries, researchers enrolled over 2,000 women with chronic HIV infection to take part in the study.

Professor Phillip Goulder from the University of Oxford said: "This research highlights the fact that HIV adaptation to the most effective immune responses we can make against it comes at a significant cost to its ability to replicate. Anything we can do to increase the pressure on HIV in this way may allow scientists to reduce the destructive power of HIV over time."

Cause of organ damage after heart attack and stroke found

Succinate, a molecule made when the body breaks down sugars and fats, can cause long-term damage to organs following a heart attack, stroke or transplant according to new research by an international team that included scientists from University College London, King's College London and Medical Research Council units.

The team behind the study hopes that new therapies will be developed to protect organs from damage following the discovery.

During a heart attack or stroke, a clot can starve the heart or brain of blood and oxygen, causing irreversible damage. Further damage occurs when the clot is dislodged and blood rushes back into the organ, and until now the reason for this was not clear.

The study, published in Nature, shows succinate accumulates at abnormally high levels inside organs when blood flow is limited. When the blood flow returns, the succinate drives the generation of harmful molecules called oxygen free radicals, which damage the cells and extend the area of injury in the organ. The scientists found succinate causes damage to a wide range of tissues in this way, so is an important target for future therapies to protect multiple organs from injury.

Initial research by the team indicates malonate esters, which are simple chemicals found in apples and grapes, could protect multiple organs from damage by blocking the production of succinate.

Professor Michael Duchen of University College London said: "I'm thrilled we've uncovered the underlying mechanisms that cause this injury, which has implications in many clinical settings. Now we plan to explore different ways to block the mechanism by which organs are damaged with the view to developing targets for new therapies in due course."

Scientists find first evidence of 'local' clock in the brain

Researchers have gained fresh insights into how 'local' body clocks control waking and sleeping.

All animals, from ants to humans, have internal circadian clocks that respond to changes in light and tell the body to rest and go to sleep, or wake up and become active.

A master clock found in part of the brain called the suprachiasmatic nucleus (SCN) is thought to synchronise lots of 'local' clocks that regulate many aspects of our metabolism, for example in the liver. But until now scientists have not had sufficient evidence to demonstrate the existence of these local clocks in the brain or how they operate.

In a new study looking at mice, researchers at Imperial College London and the Medical Research Council Laboratory of Molecular Biology in Cambridge have investigated a local clock found in another part of the brain, outside the SCN, known as the tuberomamillary nucleus. This is made up of histaminergic neurons, which are inactive during sleep, but release a compound called histamine during waking hours, which awakens the body.

The researchers deleted a well-known 'clock' gene, Bmal1, from the histaminergic neurons and found that the mice produced higher levels of the enzyme that makes histamine and were awake for much longer periods than usual. The mice also experienced a more fragmented sleep, a shallower depth of sleep, and much slower recovery after a period of sleeplessness.

This finding, published in Current Biology, indicates that there is an active clock-like mechanism in histaminergic neurons, providing evidence for the first time that local clocks work alongside the master SCN clock.

Weight influenced by microbes in the gut

Our genetic makeup influences whether we are fat or thin by shaping which types of microbes thrive in our body, according to a study published in Cell by researchers at King's College London and Cornell University.

Researchers identified a specific, little known bacterial family that is highly heritable and more common in individuals with low body weight. This microbe also protected against weight gain when transplanted into mice.

The results could pave the way for personalised probiotic therapies that are optimised to reduce the risk of obesity-related diseases based on an individual's genetic make-up.

The researchers sequenced the genes of microbes found in more than 1,000 fecal samples from 416 pairs of twins. The abundances of specific types of microbes were more similar in identical than non-identical twins, demonstrating that genes influence the composition of gut microbes.

The type of bacteria whose abundance was most heavily influenced by host genetics was a recently identified family called 'Christensenellaceae'. Mice that were treated with this microbe gained less weight than untreated mice, suggesting that increasing the amounts of this microbe may help to prevent or reduce obesity.

Professor Tim Spector of King's College London said: "Our findings show that specific groups of microbes living in our gut could be protective against obesity - and that their abundance is influenced by our genes."

Research reveals how lymph nodes expand during disease

Scientists have discovered that the same specialised immune cells that patrol the body and spot infections also trigger the expansion of immune organs called lymph nodes.

The immune system defends the body from infections and can also spot and destroy cancer cells. Lymph nodes are at the heart of this response, but until now it has never been explained how they expand during disease.

The researchers at Cancer Research UK's London Research Institute (LRI) found that when a type of immune cell called a dendritic cells recognises a threat, it makes a molecule called CLEC-2 that tells the scaffold cells within the lymph nodes to stretch out and expand. This allows an influx of disease fighting cells. It has long been known that these same dendritic cells patrol the body searching for threats and call for reinforcements to tackle them. 

Dr Caetano Reis e Sousa of LRI, said: "This important research helps us unravel how the immune system works and its role in diseases. We've shown for the first time the dual role of dendritic cells in responding to infection - both recognising that there is a threat in the body but also telling the lymph nodes to stretch out. This expansion of the lymph nodes, the command centres of the immune system, gives more room for immune cells to gather and launch their attack against infections and cancer."

Dr Sophie Acton of University College London who was visiting Dr Reis e Sousa's lab added: "We need to now see if this is the same mechanism that is used in the immune system's response to cancer and how we can exploit it to fight the disease." The study is published in Nature.

For these stories in full and to read other research news from the Crick's partners, click here.