Features

Centrioles are barrel-shaped connection hubs that, like key Meccano parts, hold together the microtubule connection rods that form the structural framework of the cells in our bodies.

As cells grow and divide, they replicate their DNA before splitting into two daughter cells. Cells also duplicate centrioles every cell division, but much less is understood about the centriole formation. And as you might expect, errors in the formation of a critical component like a centriole are implicated in a number of conditions.

Dr Ioannis (John) Vakonakis, a Wellcome Trust Research Fellow in Oxford University's Department of Biochemistry , has worked with Swiss scientists on the structure of centrioles. They have just published a study in the journal Cell that offers conclusive evidence for what makes up a cartwheel structure with nine spokes seen at the centre of centrioles. We asked him about his work:

OxSciBlog: What are centrioles and what is their role in the cell?
John Vakonakis: Centrioles are large structures that exist in most eukaryotic cells. Their primary, ancient function is to organize and serve as basis for flagella and cilia, filaments that project from the cell that are used for cell motility and sensing. However, in animal cells centrioles are also used to organize the microtubule network, a kind of ‘motorway’ system in the cell used for transporting proteins and important during cell division.

OSB: Why is it important to know how they are organised?
JV: As centrioles are important for so many different processes their number inside the cell is carefully controlled. Effects that abnormally increase or decrease centriole numbers can lead directly to medical conditions, including male sterility and cancer. We need to understand how centrioles are formed and organised in order to understand how abnormalities occur.

OSB: You describe centrioles as being based on a structure like a cartwheel with nine spokes. This seems a strange symmetry for evolution to arrive at – is there a reason, is it crucial to the centriole's function?
JV: The short answer is: We don't know! Although our data show a clear preference for 9-fold symmetry, they do not tell us why evolution ended up with this symmetry as opposed to, for example, 8-fold or 10-fold. Nor is this the only odd symmetry to be seen in this system. Microtubules, organized by centrioles in animal cells, are 13-fold symmetric! Clearly, we need more work before we can fully understand this system.

OSB: What did you show in your Cell paper?
JV: We showed that SAS-6, a protein essential for centriole duplication (a process that occurs along with DNA replication as cells grow and divide), is sufficient to create 9-fold symmetric assemblies in vitro. These assemblies are strikingly similar to the ‘cartwheels’ observed early on in the centriole formation process.

OSB: What are the implications for understanding how the centriole carries out its role?
JV: Understanding how the centriole is organized allows us to probe its properties and its role in ways simply not possible earlier. For example, we can now ask questions about how regulatory mechanisms affect the assembly process we saw with SAS-6. We can form hypotheses about how centriole formation is controlled, and then test these hypotheses in novel experiments. We could even devise means to interfere on-demand with the SAS-6 assembly process, thereby being able to ‘switch’ centriole formation on or off!

OSB: Are there any implications for human health?
JV: Modulating centriole formation is of medical interest in a number of disease conditions, including cancer. The self-assembly process we have identified in SAS-6 is a novel target for controlling cell division and growth. Thus, we believe it may be used for medical intervention through therapeutics, although clearly there is a lot of work before we can reach that stage.

An asteroid 'the size of the Titanic' caused the luminous scar on Jupiter's surface spotted back in July 2009.

In 1994 astronomers observed the planet being struck by the Shoemaker-Levy 9 comet, and most people assumed that only comets, with their erratic orbits, were likely to get close enough to Jupiter to be dragged to their doom.

Now a team, including Leigh Fletcher of Oxford University's Department of Physics, has analysed the debris and gases given off by the 2009 impact and concluded that it was caused by an object more like a rocky asteroid than an icy comet.

The researchers report their findings in the astronomy journal Icarus.

'Comparisons between the 2009 images and the Shoemaker-Levy 9 results are beginning to show intriguing differences between the kinds of objects that hit Jupiter,' Leigh told us.

'The dark debris, the heated atmosphere and upwelling of ammonia were similar for this impact and Shoemaker-Levy, but the debris plume in this case didn't reach such high altitudes, didn't heat the high stratosphere, and contained signatures for hydrocarbons, silicates and silicas that weren't seen before.'

The presence of hydrocarbons and the absence of carbon monoxide, he explained, are strong evidence for a dry object striking the planet's atmosphere instead of the expected giant hailstone.

The new finding hints that, rather ominously, Jupiter has not hoovered up all the asteroids near its orbit so that there may be other big rocks out there just waiting for their turn to make an impact.

Did you know that the humble robin uses quantum physics?

Researchers have been investigating the mechanism which enables birds to detect the Earth's magnetic field to help them navigate over vast distances. This ability, known as magnetoreception, has been linked to chemical reactions inside birds' eyes.

Now a team from Oxford University and Singapore believe that this 'compass' is making use of something called quantum coherence.

In a forthcoming article in Physical Review Letters the team report how they analysed data from an experiment by Oxford and Frankfurt scientists on robins.

The experiment showed that the magnetic compass used by robins could be disrupted by extremely small levels of magnetic 'noise'. When this noise, a tiny oscillating magnetic field, was introduced it completely disabled the Robins' compass sense which then returned to normal once the noise was removed - good news for robins which have to navigate on the long migration route to Scandinavia and Africa and back every year.

In their analysis the Oxford/Singapore team show that only a system with components operating at a quantum level would be this sensitive to such a small amount of noise.

'Quantum information technology is a field of physics aimed at harnessing some of the deepest phenomena in physics to create wholly new forms of technology, such as computers and communication systems,' said Erik Gauger of Oxford University's Department of Materials, an author of the paper.

'Progress in this area is proving to be very difficult because the phenomena that must be harnessed are extremely delicate. It would normally be thought almost inconceivable that a living organism could have evolved similar capabilities.'

Co-author Simon Benjamin from Singapore explained: 'Coherent quantum states decay very rapidly, so that the challenge is to hold on to them for as long as possible. The molecular structures in the bird's compass can evidently keep these states alive for at least 100 microseconds, probably much longer.'

'While this sounds like a short time, the best comparable artificial molecules can only manage 80 microseconds at room temperature. And that's in ideal laboratory conditions.'

Erik and Simon now hope that further research into how birds harness these quantum states could enable researchers to mimic them and help in the development of practical quantum technologies.

Erik Gauger is based at Oxford University's Department of Materials.

Seeing the interaction between antibiotics and the bugs they are designed to attack in three dimensions could help combat drug-resistant bacteria.

A team from Oxford University and Dundee University recently used the Diamond Light Source and ESRF to solve the 3D structure of the penicillin binding protein PBP3 from the bacterium Pseudomonas aeruginosa.

A report of the research is published in the Journal of Molecular Biology.

P. aeruginosa poses a particular risk to burns victims or people with a compromised immune system, for instance chemotherapy patients or people with HIV, and is resistant to most common antibiotics. The flexibility of penicillin binding proteins, such as PBP3, is key to how bacteria develop a resistance to drugs, mutating these proteins so that antibiotics can no longer ‘lock on’ to their intended targets.

By creating an accurate 3D picture of how the antibiotic binds to the protein PBP3, using X-rays produced at Diamond, the team now hope that it will be possible to develop new drugs to attack and destroy this tough bacterium.

Jingshan Ren, a member of the Oxford team, told us: 'The crystal structures of PBP3 and its complexes with antibiotics reveal how these drugs attack the bacteria in atomic resolution and provide a platform for developing new antibiotics to combat resistance using structure based drug design.'

The team included researchers from Oxford's Division of Structural Biology. 

The malaria parasite emerges and develops in synch with the bodyclock of its human host.

A study by scientists at Oxford and Edinburgh universities, published in Proceedings of the Royal Society B and covered by BBC News online and TIME has shown that the parasite suffers significant penalties if it doesn’t match its own bodyclock to the day-night pattern of its host. That is, it effectively suffers jetlag.

OxSciBlog asked co-author Dr Harriet McWatters of Oxford’s Department of Plant Sciences about the research and its implications for fighting disease.

OxSciBlog: What made you think that the malaria parasite might be able to tell the time?
Harriet McWatters: The symptoms of malaria (fever, chills) occur at regular intervals and usually at the same time of day. This is caused by the parasites emerging at the same time from red blood cells. This interval is always a multiple of 24 hours (48 or 72 hours in species that infect humans, and 24 hours in the rodent malaria we used in our study).

In order for the individual parasites to co-ordinate themselves so precisely, both with each other and the time of day, a clock must be involved.

OSB: How did you test your theory and what did you discover?
HM: We reasoned that parasites would do better when they were in synchrony with their hosts and did a very simple experiment with two separated groups of mice.

The first group was kept in a room lit between at 7am and 7 pm, the second in a room lit from 7pm to 7am. We created a mismatch between the internal clocks of the mouse and the parasite by initiating new infections in both groups in the morning, ie at lights on in room 1 and lights off in room 2.

We then watched the infections develop, counting the number of parasites in each group at regular intervals. Only half as many parasites were produced when there was a mismatch with the host’s bodyclock, or circadian rhythms.

This is very bad indeed for the parasites, as it substantially reduces their chance both of survival and of the possibility of transmission to a mosquito.

OSB: Why do the parasites emerge in the evening rather than at other times of day or night?
HM: We wanted to show that timing matters to the parasite. Clearly it does. We don’t yet know for certain why parasites choose to emerge in the evening but we have a few theories. In particular, we want to know why timing matters to the parasites: is it to evade the host’s immune system or to exploit a particular resource?

The parasites develop inside red blood cells, whose numbers peak in the evening. It could be that they time their emergence so as to make the most efficient use of a limited resource.

Alternatively, they could be trying to avoid components of the host’s immune response which are linked to the body’s circadian rhythm.

Or, it could be due to safety in numbers: if all the parasites emerge simultaneously then together they overwhelm the immune system and so increase their chance of infecting new red blood cells or a mosquito feeding on that blood.

OSB: How crucial is this timing to the survival and spread of the parasite?
HM: Our results suggest that it is very important indeed. We saw a 50% reduction in in-host replication rate. In addition, mismatched parasites produced only half the number of gametocytes. These are the reproductive stages which, when taken up by a mosquito, combine to form the next generation.

This means that the circadian mismatch is a double whammy for the parasites: it reduces by a half both the chance of survival in the host and the likelihood of transmission. This could well translate into a reduction in the ability to cause disease and for the disease to spread.

OSB: What are the implications for malaria treatments?
HM: We need to know why the parasite is so well co-ordinated with the host. It could be to shield the parasite from vulnerability to the immune system at a certain stage of its development. If so, this might make therapies more effective if they are given at a particular time of day.

OSB: Could your research improve the treatment of other infections?
HM: Although almost all organisms have bodyclocks that generate daily rhythms in behaviour and physiology, this is the first study showing the importance of circadian rhythms in host-parasite interactions.

We don’t yet know if this is a phenomenon specific to malaria or widespread among other protozoan parasites. If other parasites also need to synchronise their life cycle with their host’s daily rhythms, then developing means to weaken the parasite by disrupting this relationship could provide a new way of approaching treatments for these infections.

OSB: Are you planning further research in this area?
HM: Yes – we need to identify the mechanism by which the parasite knows what time it is. It could, for instance, be using host signals such as the rhythmic release of hormones like melatonin to tell the time or it could be responding directly to the daily pattern of light and dark. We would also like to know more about variability in timing, and whether the cell cycle can be speeded up or slowed down.