Human Stem Cells and Genetic Disease
Spinal Muscular Atrophy is a devastating inherited disease, the biggest genetic killer in infancy. New research has shown why motor neurons in the spinal cord may be more susceptible to it than other cells in the body.
Royal Holloway’s Advanced Gene and Cell Therapy lab (AGCTlab.org), led by Dr. Rafael Yáñez, have used stem cells from patients and those not affected, to study the development of human motor neurons in lab dishes.
“Induced pluripotent stem cells”, aka “iPSCs”, are as close to magic as it comes for scientists and clinicians. They can be obtained by treating cells from a skin biopsy, or a hair follicle – or almost any body part – with a few chemicals and genes in the lab. No embryos have to be destroyed, and the resulting stem cells can then be “reprogrammed” and coerced into making any cell of interest, matched to the donor. Clinicians want to use them for regenerative medicine, whereby the reprogrammed cells – for instance, pancreatic cells making insulin in the case of diabetes patients – are transplanted back into the patient with no risk of rejection. Scientists are using them to learn about development (the incredible feat of forming a human body from a single cell, which happens in every pregnancy), to learn about diseases like spinal muscular atrophy and to develop novel treatments.
Dr Yáñez’s lab have used these stem cells to produce human motor neurons, the cells from the spinal cord that control our movement and breathing, in lab dishes (see picture). Their work shows that during the process of differentiation (when cells change from stem to their final shape) motor neurons from unaffected people and patients undergo changes in gene expression similar to those happening in animal models and barely observed before during human development. These changes may go some way to explain why motor neurons are more sensitive to spinal muscular atrophy.
The research also shows how scientists are trying to reduce their reliance on animal experiments whenever possible, as stem cells now allow the production of human cells that cannot be obtained directly from patients.
For this research Dr Yáñez collaborated with clinicians and scientists from the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, the Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Evry, France and the Beckman Research Institute, California, USA. The research in Dr Yáñez’s lab was funded by the Spanish government and the Spanish Spinal Muscular Atrophy Foundation FundAME (project GENAME), the 6th EU Framework Programme (project CLINIGENE) and Royal Holloway.
This research has been published in Scientific Reports.
To find out more, please visit Rafael’s webpage.
Royal Holloway awarded funding from Join Our Boys Trust
Join Our Boys Trust has awarded major grant funding to Professor George Dickson and his research team within the School of Biological Sciences. The award will support a research programme towards a Phase 1 / 2 Clinical trial of Microdystrophin Gene Therapy.
The Join Our Boys Trust was set up in early 2014 by one family from Roscommon, Ireland, whose three young children were diagnosed with a terminal illness, Duchenne Muscular Dystrophy (DMD).
DMD is an X-chromosome recessive fatal neuromuscular disease that affects 1 in every 3,600 boys worldwide. DMD is caused by mutations in the gene that encodes for the protein dystrophin, which is vital for maintaining muscle cell structure and function. This gene defect causes progressive muscle weakness which eventually leads to loss of the ability to use all of the muscles in the body. At present, there is no effective treatment or no known cure for DMD.
The research team at Royal Holloway are world leaders in DMD research and are working towards developing a cure for DMD. The generous funds from Join Our Boys Trust will support translational research towards phase 1 / 2 clinical trials for a gene therapy treatment that could be effective in all boys with DMD. The treatment uses a virus vector to deliver a mini- or micro-dystrophin gene into muscle cells. By introducing a normal copy of the gene, protein function of dystrophin is restored.
For more information, please here.
To find out more about the Naughton family’s fight against DMD, please visit Join Our Boys.
Improving Eyewitness Judgements
Dr Laura Mickes,Senior Lecturer in the Psychology department of Royal Holloway, University of London has been awarded an ESRC grant to improve the accuracy of eyewitness identification by investigating the common identification parade procedures and features. The research will be in collaboration with Professor John Wixted of University of California, San Diego, and the grant totals a quarter of a million pounds.
The team will apply a novel method (novel to the field of eyewitness identification) to uncouple the notion of ‘response bias’ (i.e., the inclination of an eyewitness to choose someone or not choose someone from an identification parade) from discriminability (the ability to discriminate an innocent suspect from a guilty suspect). This novel technique will highlight the factors that increase discriminability during identification parades.
Thus this study has the potential to increase the effectiveness of such procedures, which could lead to more guilty people being prosecuted and fewer innocent being prosecuted.
The method used to measure discriminability is called receiver operating characteristic (ROC) analysis. ROC analysis has been used for several decades in other fields such as medical decision–making, machine learning and data mining research. ROC analysis was recently brought to the field of eyewitness memory (Wixted and Mickes 2012). In the series of studies, ROC analysis will be conducted by using eyewitness confidence ratings to measure true positive and false positive results. These results will enable the researchers to study discriminability on its own without ‘response bias’ being a confounding factor. The researchers will then be able to develop theories that explain why various identification parade procedures can change discriminability, which in turn has the potential to decrease errors (that is, decreasing the likelihood that innocent suspects will be chosen and increasing the likelihood that guilty suspects will be chosen).
This study not only involves the cognition experts (Dr Mickes and Professor Wixted), but also police investigators, solicitors, policymakers, victim support advocacy groups, victims, innocent suspects and eyewitnesses. This network of experts is essential for the success of the project, which could have a real potential impact on police procedures.
Vocal Learning in Adulthood
Dr Carolyn McGettigan, Senior Lecturer in the Psychology department of Royal Holloway, University of London, and Lab Director of the Vocal Communication Laboratory (VoCoLab), has been awarded a grant for £360,000 from the ESRC.
The award will fund a research project investigating the ability of the adult brain to acquire new speech skills. This is a collaborative project, where Dr McGettigan will work closely with Dr Marc Miquel, a consultant clinical scientist of Queen Mary, University of London. This group brings together expertise in cognitive neuroscience and MRI physics to investigate novel questions about learning and individual differences in vocal imitation skills.
As infants, we have the innate ability to learn the spoken language from our environment, and can master the pronunciation of words from multiple languages with ease. However, in adolescence and adulthood our ability to learn unfamiliar languages is limited and often a new language that is learnt will be spoken with a strong non-native accent. Dr McGettigan’s team will investigate the relationship between brain activation during learning and the behaviour (movements in the vocal tract) during learning of new speech sounds of adults.
The study will use Magnetic Resonance Imaging (MRI), to create ‘real time’ videos of the vocal tract (interior of the mouth, lips, tongue, voicebox). These videos will be combined with measurements of brain structure and function, to provide a relationship between the two during the pronunciation of new speech sounds.
This novel study of investigating brain and behaviour will provide a unique knowledge of language learning and accent acquisition. This will provide an essential foundation for potential clinical applications such as measuring and predicting learning in patients following brain injury or stroke.
Figure: Real-time magnetic resonance images of the vocal tract of a native speaker of Northern Irish English as they produce the word "bird". The sequence shows the closure of the lips for b, the positioning of the tongue for the vowel, the tap of the tongue to the roof of the mouth for d, and a return to rest. The waveform of the speech is shown below the MRI images.
To find out more please see here.
Bumblebee Social Interactions
Bumblebees are social insects; they live in a colony that is headed by a Queen. However, new research has now revealed that bumblebees are not just insects that are collective slaves to the hive.
Royal Holloway’s molecular ecology lecturer, Dr Elli Leadbeater and co-researcher Claire Florent of University College London, have studied how bumblebees use social information during the process of nectar gathering.
When it comes to foraging for food, bumblebees typically monitor the floral scents of other bee colony members inside the nest and then search for these smells outside. However, the new study reveals that bees choose to ignore the floral scents of their colony, if they had previously found another nectar-rich food source. Why bumblebees chose to stick with this personal knowledge and largely ignore the social information was not due to pre-existing biases towards certain flower colours. Rather, bees simply valued their own personally tried-and-tested nectar sources over those discovered by other bees. Individuals only made use of the “wisdom of the hive” if their favoured nectar source had run out, leaving them little option but to find new flower types.
This work was funded by the Leverhulme Trust as part of an Early Career Fellowship, and published in the July issue of Behavioural Ecology and Sociobiology (details).
To find out more, please visit Elli’s webpage.
SEARG - South East Asia Research Group
Six major oil companies including GDF Suez, Inpex, Murphy, Repsol, Statoil and Shell have signed up for the new three-year programme of the Royal Holloway South East Asia Research Group (SEARG).
SEAR is the pre-eminent geological research group in SE Asia and known internationally for its field-based studies aimed at understanding the geological development and history of the region.
Support for this academic research comes mainly from oil companies in a series of three-year consortia and the group has been led by Professor Robert Hall at Royal Holloway since 1995. Much of the work is carried out in collaboration with partners in the UK, Europe, SE Asia and Australia. Successful collaborations with SE Asian universities and government institutions particularly in Malaysia and Indonesia, which include training of MSc and PhD students at Royal Holloway, have been important. The research programme at Royal Holloway currently includes:
sedimentary provenance studies
a variety of thermochronological projects
U-Pb dating of zircons
structural geological work on faults and active fold and thrust belts
geochemistry of modern volcanoes
i nterpretations of mantle structure
An important product has been tectonic and palaeogeographic reconstructions of the SE Asian and SW Pacific region and computer animations, that are comprehensible to almost anyone and help to explain the implications of geological change for issues such as sediment supply, magmatism and mineralisation, ocean circulation, global climate, and distribution of plants and animals. They are widely cited and used by geoscientists and life scientists, but are also used by museums, in teaching at all levels and many countries, and by the media, commonly after major geological events that capture international attention such as volcanic eruptions, earthquakes and tsunamis. They are freely available from the SEARG web site .
The current programme has a budget of over £2 million pounds. Company members value the programme and meetings where they discuss results with the team for example: “Projects have involved commitments of several hundreds of millions of dollars in exploration since 2008, so the work of SEARG in providing good solid geological information in this region has been vital to this effort”.