Tag Archives: Science Week

Science Week: Piecing together the jigsaw of climate change and human evolution

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

Dr Phil Hopley, of Birkbeck's Department of Earth and Planetary Sciences

Dr Phil Hopley exhibited replica skulls of our ancestors during Science Week. Photo: Harish Patel

I knew an unusual presentation was in store as soon as I saw six skulls menacingly positioned at the front of the lecture theatre. The exhibits – all different shapes and sizes – immediately caught the audience’s attention, and our questions about their origins were answered in the fascinating hour that followed.

Dr Phil Hopley began Birkbeck’s series of Science Week lectures with a talk on 16 April about the links between climate change and human evolution. He used the skulls – five replicas of our ancestors and one gorilla skull – to illustrate how evolution is all about the changing dimensions of the head as it has become rounder and larger to accommodate a bigger brain over millions of years. In comparison, the gorilla’s skull includes ferocious canines and space for huge powerful jaws – it certainly sent a shiver up my spine being only a few feet away from my seat.

A family tree dating back millions of years
Dr Hopley, of Birkbeck’s Department of Earth and Planetary Sciences, explained how the last common ancestor of chimpanzees and modern humans was on this planet about six of seven million years ago. Both branches of the family tree then developed separately, with chimpanzees on the one hand, and about 20 species of hominins – the ancestors of modern humans – walking on two legs on the other. As the hominins evolved, they became characterised by their tool use, larger brains, language and art, eventually developing into Homo sapiens – our own species. But our ancestral line has not been straightforward, and Dr Hopley highlighted the complexity. He said: “Homo sapiens is the only human species alive today, but for most of human evolution there have been a number of co-existing human species.”

As Dr Hopley explained, hominin fossils have mainly been found in two areas – the Rift Valley in East Africa (dating back five million years), and caves in Southern Africa (dating back 2.5 million years). Yet, hardly surprising, given the awesome amount of time involved, it is very rare to find a whole hominin specimen. What is clear is that the human fossil record is very incomplete, both geographically and temporally, and solving the mystery is a bit like piecing together a jigsaw.

Climate change: from forest to grassland
The question of why our ancestors evolved to become bipedal was then addressed, and this was where Dr Hopley referred to his work studying fossils from caves in South Africa. The study of carbon and oxygen isotypes and climate modelling has shown that the savannah in Africa developed eight million years ago due to the reduction in carbon dioxide and reduction in rainfall. As the grasslands replaced the forests, our ancestors evolved to walk on two feet as they needed to cover large distances to search for food, which wasn’t necessary when they were still living in the forest. Although it’s difficult to build up a comprehensive understanding of how climate change drives evolution, Dr Hopley did present a general conclusion. He said: “Human evolution did occur because of climate change in the broad sense as forests were replaced by savannah.”

I’ve never been to a lecture with skulls on display before and I’ll certainly never forget this one. It was a powerful way to remind us that our common ancestors adapted to the African bush and started walking when the forests began to recede.

BabyLab Showcase 2012

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This post was contributed by Denise Breitenbach and Yvonne Whelan 

Introduced by Prof. Mark Johnson, this year’s Birkbeck BabyLab Showcase highlighted the importance of researching aspects of infant cognition over time. Between birth and adolescence, our grey ‘jelly-like’ brains expand three times in size and undergo an astounding amount of structural adaptation. These changes aren’t solely reliant on our genes: genetic information unfolds over time by interacting with our external world experiences. For example, social skills related to the processing of facial cues such as smiling, develop early on as children experience seeing others’ faces. Early life contextual factors can also impact negatively upon development: poverty has been linked to effects on the brain which can result in a range of mental health difficulties.

So how are BabyLab scientists linking structural brain changes to the development of perceptual, cognitive, motor and language abilities? As babies often lurch rapidly between contented gurgling, gutsy wailing and gentle snoozing, novel experimental techniques are required. These include: 1) Behavioural testing such as eye tracking (e.g. used for testing preferential looking at faces versus complex objects) 2) Electromagnetic recording methods (EEG/ERPs) using a damp hat to record tiny voltage changes on the scalp as groups of neurons synchronously fire together on exposure to a task 3) Optical imaging (NIRS), where weak light beams are used to track blood flow in the brain as babies are thinking/perceiving stimuli 4) MRI scanning – used for sleeping babies to discover more about brain structure and functioning.

Changing their mind

In the first showcase talk, Dr Natasha Kirkham explained how good working memory (WM) and inhibitory control (IC) in children contribute to the development of decision-making, remembering of rules and the production of contextually appropriate behaviour  (e.g. speaking loudly in assembly, but not at the cinema). Childhood development of WM and IC has been tested using the Dimensional Change Card Sort Task where firstly, children were asked to match a target card with reference stimuli according to shape, and then to only match according to colour. Although 3 year olds performed worse than 5 year olds where there was a category conflict according to the prior rule (e.g. a red truck had to be matched with a red star), scaffolding a 3 year old child’s learning experience helped to improve their performance. For instance, instructing them to repeat a new rule, rather than solely providing ‘yes/no’ feedback to card choices delivered the greatest improvement. Next, Natasha provided us with an additional experimental example testing WM and IC – the ‘Delay of Gratification Task’ where in order to earn many more Oreo cookies, children were asked to refrain from eating those already placed before them until an adult re-entered the room. Amusing strategies employed included children sitting on their hands or putting cookies in drawers!

Shining Light on the Infant Brain

In the second showcase talk Dr Sarah Lloyd-Fox informed us how an exciting and novel way to shine light on the functioning of an infant’s brain is to do it literally by using a technique called NIRS. This works by shining a weak light into the infant’s head which passes through the infant’s skull and reaches underlying brain tissue.

NIRS comes with many benefits to researchers: it can be used on babies who are awake (so they can be tested with visual imagery rather than sounds only) and has better spatial resolution than MRI. At Birkbeck, NIRS has been used to investigate when infants start to see and interpret actions, alongside questions such as ‘is our ability to use our hands to interact with our environment related to how we respond when we see other people performing similar actions?’. As emphasized by Dr. Natasha Kirkham earlier, the experimental value of play should never have been underestimated and this question was examined using games testing infants’ manual expertise. Intriguingly enough, evidence suggests that there may be a relationship between the way our developing brain responds to the sight of human motion and the motion we learn to form ourselves.

Infant time perception – ‘Escaping the Eternal Now’

In the third talk Dr Caspar Addyman highlighted how babies are often absorbed in something in the ‘now’: “in one moment babies can be in howls of tears and the next, in peals of laughter”.

How is it that humans gauge how quickly an event ‘feels’? Caspar described how for adults the longer ago something occurred, the fuzzier a memory exists of it. Judging the ‘fuzziness’ gives us a measure of how long ago in time it occurred. Since infants’ memories are not very well developed, it is difficult for them to judge the continuity of events. Thus, in order to learn more about the development of infants’ perception of time, BabyLab researchers are testing the long and short term memories of 6, 10 and 14 month olds using habituation (the classic technique of making babies bored!) with heart rate measures and eye movements being monitored. In addition, movement is thought to be very important to an infant’s developing understanding and judgement of time and events – at 6 months the world has to come to you, by 14 months exploration increases as crawling and walking ensue, expanding an infant’s sphere of the world. Such interaction may link to changes in the judgement of time. This is ongoing research and we look forward to hearing the results of Caspar’s study in the future.

Autism in infancy

The final talk, given by Dr Teodora Gliga, described the progress developmental science is making towards understanding autism spectrum disorders (ASD). ASD are presently diagnosed from 24 months onwards when children fail to meet social communicative developmental milestones. Researchers at Birkbeck are investigating how ASD can be detected and diagnosed earlier, for example by trying to decipher the pre-requisites for language development. As ASD is a genetic disorder (there is a 10% chance of developing ASD if one has a sibling with it vs a 1% chance for the general population), a prospective longitudinal study has been used to investigate infants who have siblings with autism over a 3 year clinical assessment period. 

Evidence indicates that although there are no differences in paying attention to faces between ASD and typically developing infants at 6 months and 12 months, there are early differences with gaze direction and a failure to follow gaze from 6 months – a precursor of social ability. In order to inform intervention strategies, future studies will need to focus on testing children at multiple time points and using measures such as attention (looking away from irrelevant objects), the ability to discriminate gaze direction, follow gaze, to acquire words,  maternal input (words child hears), the social and biological environment, a child’s genes, and risk factors during pregnancy.

Read more about BabyLab research in the news.

Birkbeck Commemorates World TB Day by Discussing Drugs from Plants

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This post was contributed by Clare Sansom, a part-time lecturer in Birkbeck’s Department of Biological Sciences, and a freelance consultant and science journalist.

World TB Day is held on 24 March every year, to mark the day in 1882 when Robert Koch, one of the fathers of microbiology, first announced that he had discovered the cause of tuberculosis (TB) – the bacterium now known as Mycobacterium tuberculosis. Over 125 years since its discovery, and despite billions of dollars of investment in drug discovery, this bacterium is still a killer. The World Health Organisation estimates that about two billion people are infected with latent tuberculosis; in 2010, the last year for which full figures are available, over eight million people became ill with active tuberculosis, and 1.4 million people died from the disease. Two factors help make TB particularly deadly: it often occurs in people infected with the HIV virus, where it is one of the major causes of death, and drug resistant forms are becoming more common. In January 2012, Nature reported the identification in India of so-called “totally drug resistant” (TDR) tuberculosis, resistant to all anti-TB drugs in general use.

In 2012 at Birkbeck, World TB Day coincided with the start of the College’s annual Science Week. Dr Sanjib Bhakta, head of the Mycobacteria Research Laboratory in the Department of Biological Sciences, organised a well-attended symposium on tuberculosis and its treatment. Besides two scientific presentations, the symposium featured a short video, Tuberculosis: The Real Story, highlighting the views of people affected by TB in the UK, and a panel discussion led by the grassroots volunteer organisation Results UK on some of the political challenges raised by tuberculosis. 

Both science lectures focused on plants as a source of potential new drugs for tuberculosis. Professor Franz Bucar from the University of Graz in Austria highlighted the extreme chemical diversity of compounds that could be extracted from plants, particularly as compared to those found in the average synthetic compound library. Plants have always existed alongside their own microbial pathogens and have evolved natural antibiotics to protect themselves. Our ancestors, before the dawn of scientific medicine, used plant extracts to treat infectious disease, often quite successfully. The sub-discipline of ethnomedicine involves “mining” these traditional or historical remedies for pure chemicals that can be developed as, or modified into, drugs.

Bucar described a European herb, elecampane or Inula helenium, which is known to have been used to treat lung disease in the sixteenth century. He explained how a complex mixture of natural products derived from this plant had been tested against mycobacteria. Compounds found to have anti-mycobacterial activity were extracted and purified. Other plants have also yielded useful lead compounds; extracts of bark from a small tree with the Latin name of Berchemia discolor have even been shown to inhibit multi-drug resistant strains of Mycobacterium tuberculosis at useful concentrations.

Discovering antibacterial products in plant extracts, however, is only a first step towards drug discovery. Even when natural products like these compounds are found to be selective for bacterial over human cells, it is necessary to discover their mechanism of action; to modify them to optimize their activity; and, since plant sources are often scarce and extraction processes costly, to determine methods of synthesizing them in the laboratory.

The second scientific presentation was given by Dr. Bhakta himself and described current work in Birkbeck’s Mycobacteria Research Laboratory in searching for potential drugs for TB. These are needed not only to combat resistant forms of the bacteria but to improve current treatment regimens for “standard”, drug-sensitive TB. This requires a combination of four drugs to be taken for two months followed by two drugs for another four months, and many patients, particularly poorer and less well educated ones, fail to complete such a long and complex regimen. This in turn can lead to the development of further resistant strains.

Ideally, new drugs are required that target proteins not targeted by existing drugs, as resistance will be harder to develop. Mycobacteria have extremely complex cell walls, unlike those of other types of bacteria; they are essential for the bacteria to survive, and the enzymes used to synthesise them have no equivalents in mammalian genomes. These enzymes, therefore, have many of the characteristics of excellent drug targets.  Bhakta and his group have been exploring ways to inhibit the synthesis of the peptidoglycan that is one of the most important constituents of that cell wall. This molecule has been described as the bacterium’s “Achilles heel”, but no drugs targeting its synthesis have yet entered the clinic.

Mycobacteria synthesise peptidoglycan via a series of enzymes known as ligases, each of which adds a new link to the growing peptidoglycan chain. Bhaka’s group has focused on one of these ligases, termed MurE. This enzyme is essential for the bacterium to survive and it is conserved in all Mycobacterium tuberculosis strains. Working in collaboration with Professor Nick Keep, also in the Department of Biology, Bhakta solved the structure of MurE and showed it to have an active site that could in theory, at least, be occupied, and blocked, by a relatively small, “drug-like” molecule. He and his co-workers are now searching libraries of natural products for compounds that might inhibit this enzyme. They have identified promising MurE inhibitors from plants endemic to both Colombia and China, and are synthesizing analogues of these compounds for further testing.

It is unlikely that the next generation of anti-tuberculosis drugs will include any unchanged natural products. It is extremely likely, however, that natural products will yield the “scaffolds” on which these desperately needed drugs may be built, and perhaps one of these will be generated from within Bucar’s or Bhakta’s groups.

Under the Microscope: Kinesin Motors and Cancer

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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.