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MRC Harwell 2017 Festival events

For the 2017 Festival of medical research we will be having two events at MRC Harwell: a Year 12 Open Day and a Patient Open Day. See below for more information about these two events. 

Year 12 Open Day – Wednesday 21st June 

This event is aimed at students who are interested in a career in biomedical research. On their visit, they will have the opportunity to find out about genetics research, how mice are used to study disease, and the different types of careers in biomedical science. The visit will include a lab tour, a practical scientific skills session, a careers fair, and a visit to our world class animal facility – the Mary Lyon Centre. 

Patient Open Day – Friday 23rd June 

For this event would like to invite patients, their families, and representatives who are interested to find out more about primary scientific research, the relationship between genes and disease, and how mice are used in medical research. The visit will include an interactive tour of our working scientific laboratories, a first-hand opportunity to talk to scientists, and a visit to our world class animal facility – the Mary Lyon Centre.  

Please note this open day is not disease or condition specific, we will therefore not be able to offer clinical advice. 

To apply

Please note, for both events there is a morning and an afternoon session. Places are limited. If you are interested or would like more information please email us at openday@har.mrc.ac.uk

                                                                                               

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MRC Harwell 2017 Festival events

For the 2017 Festival of medical research we will be having two events at MRC Harwell: a Year 12 Open Day and a Patient Open Day. See below for more information about these two events. 

Year 12 Open Day – Wednesday 21st June 

This event is aimed at students who are interested in a career in biomedical research. On their visit, they will have the opportunity to find out about genetics research, how mice are used to study disease, and the different types of careers in biomedical science. The visit will include a lab tour, a practical scientific skills session, a careers fair, and a visit to our world class animal facility – the Mary Lyon Centre. 

Patient Open Day – Friday 23rd June 

For this event would like to invite patients, their families, and representatives who are interested to find out more about primary scientific research, the relationship between genes and disease, and how mice are used in medical research. The visit will include an interactive tour of our working scientific laboratories, a first-hand opportunity to talk to scientists, and a visit to our world class animal facility – the Mary Lyon Centre.  

Please note this open day is not disease or condition specific, we will therefore not be able to offer clinical advice. 

To apply

Please note, for both events there is a morning and an afternoon session. Places are limited. If you are interested or would like more information please email us at openday@har.mrc.ac.uk

                                                                                               

Attachment(s): 

Gene found to play prominent role in central nervous system foundation and function

Researchers at the MRC Harwell Institute have gained new insights into the function of the gene Katnal1. Katnal1 is one of a small family of genes that have been linked with intellectual disability, autism and schizophrenia in humans. In mice, loss of function of the gene leads to poor learning and memory while the growth, migration and shape of neurons in the brain are all disturbed. This research highlights Katnal1 as a prime candidate for further study of the mechanisms underlying diseases of cognitive dysfunction.

We have approximately one billion nerve cells in our brain. These neurons form a complex architecture of networks, which communicate with each other and with other areas of the body through chemical signals. Very early in development, neurons migrate from their birthplace to their final destination in the brain. During this period they develop and form numerous elaborate branches enabling crucial connections to be made with many other neurons. Defects in these processes have been associated with many cognitive disorders.

Image at top shows neurons in normal mice (left) and mutant mice (right). In the mutant mice it can be seen that the neuron branches are shorter and thinner. The gene Katnal1 codes for a protein which determines the shape of microtubule structures within cells. In neurons, microtubules are important for directing neuronal migration and branching. Katnal1 and its family of genes enable the reshaping of microtubule structures at the appropriate time in developing neurons and the termination of branch growth so new ones can be formed.

This gene previously has not been well characterised, although in a small patient study loss of the gene was related to intellectual disability while one rare gene alteration has been linked to schizophrenia.

In this study, mice with a coding sequence error in Katnal1 were identified as part of a large scale genetic study. The error, or mutation, resulted in a non-functional gene – it was essentially ‘switched off’. When the behaviour of the (mutant) mice was compared to normal mice (with the correct gene) a range of behavioural abnormalities were seen including poor learning and memory.

Changes in the brain, detectable only at a microscopic level, seemed to underlie these behavioural disturbances. Analysis of different brain sections showed that the patterns of neurons in the hippocampus (a region of the brain associated with memory) and cortex (the outermost layer of the brain) were different in mutants. The cortex has well defined cell layers so anomalies are easy to spot. More neurons were seen in the outer layers of the cortex in mutants, suggesting that the neurons may have migrated too far.

Furthermore the neurons from mutants had a different shape and fewer synaptic spines – these are the structures on neurons that enable communication with other neurons.

Defects were also seen in the cilia of the mutant mice. Cilia are hair-like protrusions that stick out from all cells and are vital in early development. In the brain cilia are thought to maintain the circulation of chemicals and nutrients in the cerebrospinal fluid – a colourless fluid which maintains a healthy environment for the brain and its neurons. Defective cilia have been linked to many brain disorders including intellectual disability.

Dr Pat Nolan, one of the authors on the paper, commented:

“Our findings highlight the importance of this small group of genes in establishing the neuronal connections that are critical for precise brain functions”.  

Further study of this gene and its role in neuron growth and development may provide insight into the cognitive dysfunction underlying intellectual disability and conditions such as autism. This will increase the likelihood of being able to identify therapeutic targets and potential treatments in the future.

To read the research in Molecular Psychiatry click here

Images show neurons in normal mice (left) and mutant mice (right). In the mutant mice it can be seen that the neuron branches are shorter and thinner. 

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CRISPR/Cas9 Quality Control

Joffrey Mianné and colleagues at the MRC Harwell Institute have published new research in Elsevier Methods outlining their proposed protocols for effectively screening the results of CRISPR/Cas9 gene editing technology. 

CRISPR/Cas9 is a new gene editing technology that has revolutionised research in the field. The technology allows for faster, cheaper, and more precise gene editing than was previously possible. It is increasingly used in the field of mouse genetics to help study the relationship between genes and human disease. It is now the chosen method for the International Mouse Phenotyping Consortium (IMPC), a global project to identify the function of every gene in the mouse genome.

Despite the acceleration of the technology – the results obtained with CRISPR/Cas9 can often be unpredictable. Frequently the genetic change made is not present uniformly throughout the organism (known as mosaicism) and other unwanted changes can be found at the site where the gene has been altered. It is essential that mice taken forwards carry only the desired change so that any physiological changes seen are because of that and not something else on the genome. The ability to correctly select mice with the desired mutation requires robust and accurate methods.

The technology allows many types of genetic changes to be made, including deletions and even swapping the individual molecules making up the code of the DNA. Here the researchers have proposed a framework to analyse the results of CRISPR/Cas9 activity according to the type of genetic alteration intended. They have ascertained that due to the high level of unpredictability in the first generation it is better to definitively characterise the following generation and establish the mutant mouse line from there.

This research will contribute to the current debate on best practice for the use of CRISPR/Cas9 in biomedical research.

How CRISPR/Cas9 works

The CRISPR-Cas9 system is made up of two key molecules – the enzyme Cas9 and a piece of guide RNA. In brief, the guide RNA locates and binds to the target DNA where the change is going to be made. Its sequence is complementary to that of the target DNA. The Cas9 then acts as molecular scissors and makes a cut across both strands of DNA in the double helix. The cell then recognises that the DNA is damaged and attempts to repair it. Scientists have been able to harness the cell’s own DNA repair machinery to introduce changes into the genome.