Category Archives: Science

Under the Microscope: Kinesin Motors and Cancer

Leave a reply

This post was contributed by Jill Faircloth, an alumna of the Birkbeck Structural Molecular Biology MSc

There are many different types of cancer but each is caused by the failure of a cell to control its normal healthy cell division.  Uncontrolled proliferation produces a cluster of cancerous cells, a tumour, often the first indicator of many cancer types.  Several prevalent cancer drugs target microtubules, which are used by the cell to orchestrate the intricate ballet of cell division, but disabling this machinery provokes various unpleasant associated side effects.  In this lecture, which was part of Science Week, Dr Carolyn Moores, of the Department of Biological Sciences at Birkbeck shared some exciting recent developments in her work which pave the way for new cancer drugs which are less toxic to the rest of the body.

To understand the size of the machinery under discussion, if a human body were amplified to fill the whole of Buckingham Palace, each cell would be approximately the size of a single grain of sand.  These cells need to replicate, both to grow and to repair normal wear and tear and this replication is a delicate and highly regulated process.  Dr Moores showed a video of a dividing cell, taken from a remarkable online library of cellular images.  This process starts with the separation of the chromosomes, the familiar four legged bearers of our DNA, of which there are 23 pairs in humans.  The chromosomes arrange themselves in the centre of a spindle-like framework, which then retracts in opposite directions, separating each chromosome into halves and grouping them into two new nuclei centres, ready for the division of the rest of the cell. 

The dynamic spindle framework at the heart of this incredibly accurate mechanism is primarily composed of microtubules along with associated proteins including members of the kinesin family of molecular motors, which organise them.  Microtubules are made up of pairs of tubulin molecules, or dimers, each of which has a polar structure.  The dimers bind to each other both longitudinally, with opposites attracting so that the overall polarity is maintained, and laterally so that long thin stable cylinders are formed.  These cylinders can grow and shrink with great flexibility and at all lengths the cylindrical structure provides a frame which can withstand the tension required in pulling chromosomes apart.  Drugs that block the dynamics of microtubules can therefore block the ability of cells to proliferate, which is why they are used in chemotherapy.  Unfortunately, microtubules are also critical in healthy cell repair, as well as providing frameworks essential for cellular structure, organelle positioning and vital transport networks within the cell.

Kinesins are highly attractive as potential targets since each appears to operate primarily in support of one of the major microtubule functions, in which case an inhibitor could be designed to attack the cell’s ability to divide without affecting its other vital processes.

Kinesin proteins comprise several domains, one of which is the motor domain, responsible for the protein’s movement.   This motor binds to a microtubule and uses it as a track with a directionality given by its polarity.  It also binds ATP, the universal cellular fuel, which provides the energy required to move along the track.  This has been particularly well studied in kinesin 1, whose function is to transport cargo along the microtubules.  In a mechanism that Dr Moores compared to a child walking on his hands, each unit of cargo is transported by a linked pair of kinesin 1 molecules.  The molecules alternate so that one will bind to the microtubule and the energy source, ATP, and then its partner will displace it so that the motor effectively steps hand over hand along the microtubule track.  Structural studies of kinesin 1 bound to a microtubule show that a small linker region of each kinesin reacts with the polarity of the track to point and presumably inform the direction of travel.

Dr Moores’ group are studying kinesin 5, which combines into oligomers of four molecules and forms crosslinks between microtubules.  This has been shown to be essential to cell division in humans.  The structural studies have involved cryo electron microscopy which has given a 3D model of the motor domain of kinesin 5 bound to a microtubule, both binding ATP and without ATP present.  Electron microscopy is a technique much like ordinary microscopy except that an electron beam is used instead of visual light and this gives images at a molecular level.  The fact that a fast freezing method is employed is extremely useful since biological samples are effectively viewed in solution, as they are in their natural state.  By fitting x-ray crystallography models, which give atomic level detail of smaller molecular configurations, into the 3D cryo electron microscopy models, an enormous level of detail is obtained.

Drugs that target kinesin 5 are currently in clinical trials and appear to be successful so far.  It would appear that the drugs interact with an on/off switch elucidated by Dr Moores’ team but at the moment the precise function of the on/off switch is not known.  Work continues in this rewarding area of study with the aim of understanding the purpose of the on/off switch and consequently being able to design future cancer drugs which have even higher specificity and consequently better outcomes.

More details of Dr Carolyn Moores’ work are available on her staff page.

Damage assessment of heritage objects and methods used in their preventive conservation. A talk by Dr Marianne Odlyha.

Leave a reply

This post was contributed by Bryony Stewart-Seume, a Senior Administrator in the School of Science.

Science Week continued with a lecture given by Dr Marianne Odlyha, concerning ways in which heritage objects can be damaged over time, and recent research into the methods which can be employed to minimise risk and decay. The lecture was well attended and well received.

After being introduced by Professor Nick Keep, the Dean of the School of Science, Dr Odlyha gave some background to the project on which she has been working for some time; “Measurement, Effect Assessment and Mitigation of Pollutant Impact on Movable Cultural Assets – Innovative Research for Market Transfer.” Essentially this research looks at the different environments in which moveable cultural objects (paintings, artefacts, tapestries, etc…) are displayed, stored or transported and to what pollutants these conditions may subject the objects.

Dr Odlyha began by explaining that the research is an interdisciplinary area; it encompasses many academic fields ranging from Art History to hardcore Science. The key objective of the work is to retard the degradation and decay of objects as much as possible. A description of the corrosion found in the organ pipes in the St James Church in Lübeck, Germany was given as a case study, and as an example of a situation that could have benefitted greatly from better environmental monitoring systems.  The organ is now sadly in a terrible state, and is unplayable.

It is of course unfortunate that the material of choice for the construction of organs (oak) is a high emitter of damaging gases. This issue is exacerbated by the fact that organs (and other such items of cultural worth) are often located in places with central heating, which is there for the comfort and convenience of the audience.

I was surprised that, despite being a method of display for many years, even something as apparently innocuous as the wood from which a case is built can cause damage over time. Plywood, for example, gives off very strong emissions; of course the cases in which paintings are kept in storage (Dr Odlyha used the example of the Tate’s store to highlight her point) are primarily built from this material. There is a legitimate economic reason for this, but perhaps this is offset against the damage potential?  While showcases will keep out much of the outside pollutants, it seems that it is just as important to be aware that the climate on the inside will also have a noticeable effect on the item on display.

Similarly, the practice of using varnish on a painting is an old one, and was originally thought to do some good. It does have the effect of darkening the image and enhancing colour saturation; however, as Dr Odlyha told us, over time the painting may start to yellow. It is not only the varnish itself that can inflict damage on the painting, but also the method of cleaning employed. It is also important to know that when we find a solution that minimises the damage potential of one polluting factor, we may have merely introduced another. The cycle of material selection/damage dealt is apparently perpetual, and it is only through cutting edge, up to the minute research that we can hope to do what can be considered best for our heritage.

There are options, though, for mitigating the risks to movable objects; one of those being a so-called ‘Micro-Climate Frame’. The conditions on the insides of the frames are measured using custom-made dosimeters and compared with the ambient atmosphere. Fluctuations in the surroundings have proven to be far more severe than within the frames themselves. Of course this is good news, and what is expected, but Dr Odlyha admitted that there is still much research to be done in this area.

You can find out more about Dr Odlyha’s research at http://www.memori-project.eu/memori_project.html

Eye-tracking technology: Understanding what we really see

Leave a reply

This post was contributed by Guy Collender from Birkbeck’s Department of External Relations.

Our eyes are imperfect, but we don’t notice their limitations. This reality and its implications for artists and film-makers were clearly shown during a Science Week lecture at Birkbeck.

There was audience participation too, as the eye movements of volunteers were tracked with high-speed infrared cameras to prove what happens when people look at pictures and films.

Dr Tim Smith, of the Department of Psychological Sciences at Birkbeck, shared his research during the talk, including his work with Tate Britain to help restore a famous painting.

He began his talk on Wednesday 29 March by outlining the theory of vision science – the study of how people view, perceive and remember visual scenes, and how this influences their actions.

In practice, our eyes often fail to detect changes in the background because they can only focus on a small proportion of the visual field and process a limited amount of information. This “phenomenon of change blindness” is significant as it means viewers can be distracted from what is happening. Smith said: “What we think we see is rarely actually what we see.”

A masterpiece restored

Destruction of Pompeii and Herculaneum by John Martin

Destruction of Pompeii and Herculaneum by John Martin

Art and science are often closely linked, and Smith demonstrated how he has applied insights from vision science to inform art conservation.

In 2010, Tate Britain decided to attempt a restoration of the flood-damaged 19th century masterpiece Destruction of Pompeii and Herculaneum by John Martin. A large section of the dramatic painting, which documents the eruption of Mount Vesuvius, was lost, and Smith was asked for his expertise to recommend how to remedy this. He used eye-tracking equipment to assess how viewers would look at four prototypes of restored versions of the painting: fully restored, restored but with less detail in the filled section, muted colour in the filled section, or a neutrally coloured infill.

His findings showed that the eyes of viewers were drawn to the edges of the lost section when it was filled with a muted or neutral colour, and this detracted from the original intention of the artist as this was where the mouth of the volcano was supposed to be.

Informed by Smith’s research, Tate conservator Sarah Maisey embarked on a reversible reconstruction of the lost section. Some detail was omitted in the reconstructed section, allowing viewers to see the entire main content of the painting while spending most of their time viewing the original sections. The painting was exhibited during the recent John Martin Apocalypse exhibition at Tate Britain, and Smith said the reaction to the restoration was “overwhelmingly positive.”

Cinematic continuity
Smith continued by demonstrating how gaze patterns generated by eye-tracking technology also show how people watch films. He outlined the history of film and editing conventions, and explained how film-makers replicate the way people attend to, and perceive, reality. This includes focusing on motion, helps lead to a seamless representation, and means that edits largely go unnoticed in today’s films, where the average duration of a shot is only 2.5 seconds. Smith added: “If we compose edited sequences according to these conventions, we can make viewers blind to a large proportion of the actual cuts.”

Astrobiology: The search for life on Mars and beyond

Leave a reply

This post was contributed by Guy Collender from Birkbeck’s External Relations Department.

There might be life on planets other than Earth, but it hasn’t been discovered yet and Birkbeck scientists are playing their part in the search.

This quest, the awe-inspiring enormity of the universe and the Earth’s 4.5 billion-year history were all discussed at a fascinating lecture as part of Science Week.

The talk on Tuesday 27 March was delivered by Dr Ian Crawford, of the Department of Earth and Planetary Sciences, at Birkbeck.

He mentioned how Birkbeck’s expertise is contributing towards the European Space Agency’s mission to land a spacecraft on Mars and drill below its surface. Dr Claire Cousins is involved through her work at the UCL/Birkbeck Centre for Planetary Sciences in the scientific development of the camera for the ExoMars rover.  

Dr Claire Cousins, of UCL/Birkbeck Centre for Planetary Sciences, carrying out experiments in the Arctic. Photo credit: Kjell Ove Storvik

Dr Claire Cousins, of UCL/Birkbeck Centre for Planetary Sciences, carrying out experiments in the Arctic. Photo credit: Kjell Ove Storvik

Crawford began by explaining his life-long interest in astrobiology – the science of trying to find life elsewhere in the universe based on the history of life on Earth. He said: “The Earth, as far as we know, is the only inhabited planet in the universe. What we know about life on Earth must inform our search.”

Life on Earth
A timeline was set out to show the history of the Earth and the slow evolutionary development of life upon our planet.

Following the birth of the Earth 4.5 billion years ago, its surface was bombarded by giant meteorites and its oceans were vapourised for the first few million years. This was followed by the emergence of a warm, wet and rocky planet – all necessary conditions for supporting life.

As a result, micro-organisms were born about 4 billion years ago. The transition from such origins of life to complex lifeforms took many millions of years, with multi-celled animals similar to “jellyfish” only appearing 600 million years ago.

Today there are thousands of planets across the universe that resemble the Earth as it was when it began to support life 4 billion years ago. This fact led Crawford to predict that microbial life might be common elsewhere in the universe, but multi-celled animals and intelligent life might be rare.

Searching for life on Mars
The history of Mars exploration followed, including details about the six spacecraft that have landed on the red planet. The dried-up river valleys on Mars indicate that rivers did exist in earlier times, leading Crawford to suggest that it was an “inhabitable” planet in the past.

He said: “There is no doubt that Mars was a warm, wet and rocky place, exactly the kind of place that life should have evolved upon.” Today’s Mars is inhospitable due to its the cold temperatures (-60 degrees), no ozone layer, and its red, dusty surface.

Despite finding nothing so far, the search for whether Mars supports life now, or ever did in the past, continues. The Mars Science Laboratory robot is due to land on the red planet this August, and the plan is for the ExoMars rover to follow suit in 2018.

Future space exploration
Crawford added that there will be no definitive answers about current or past life on Mars until field geologists step foot on the planet, and this remains years away. In response to a question, Crawford said that sending humans to Mars might, technologically, be possible by 2030 (more likely by 2060), but this would be unlikely because of economic and political considerations.

He also spoke about the need for better telescopes, and other potentially inhabitable parts of the solar system, including Europa – one of Jupiter’s moons – and Enceladus – one of Saturn’s moons.

Extraterrestrial intelligence
The question of aliens was also addressed, with Crawford saying that it is unlikely that extraterrestrial intelligence will be discovered, especially as nothing has been discovered since the search began 50 years ago. Whereas finding multi-celled animals elsewhere in the universe might be rare, finding lifeforms capable of sending technology might be even rarer. He said: “I think the galaxy looks like a quiet place.”

Despite finding nothing so far, Crawford stressed the importance of continuing to search for life in the universe.