All posts by Katarzyna
Mild myopathy in mouse models of skeletal diseases – research paper
Abstract
Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are skeletal disorders resulting from mutations in COMP, matrilin-3 or collagen IX and are characterised by short-limbed dwarfism and premature osteoarthritis. Interestingly, recent reports suggest patients can also manifest with muscle weakness. Here we present a detailed analysis of two mouse models of the PSACH/MED disease spectrum; ΔD469 T3-COMP (PSACH) and V194D matrilin-3 (MED). In grip test experiments T3-COMP mice were weaker than wild-type littermates, whereas V194D mice behaved as controls, confirming that short-limbed dwarfism alone does not contribute to PSACH/MED-related muscle weakness. Muscles from T3-COMP mice showed an increase in centronuclear fibers at the myotendinous junction. T3-COMP tendons became more lax in cyclic testing and showed thicker collagen fibers when compared with wild-type tissue; matrilin-3 mutant tissues were indistinguishable from controls. This comprehensive study of the myopathy associated with PSACH/MED mutations enables a better understanding of the disease progression, confirms that it is genotype specific and that the limb weakness originates from muscle and tendon pathology rather than short-limbed dwarfism itself. Since some patients are primarily diagnosed with neuromuscular symptoms, this study will facilitate better awareness of the differential diagnoses that might be associated with the PSACH/MED spectrum and subsequent care of PSACH/MED patients.
The full paper can be seen here
Or downloaded here: myopathy paper
9th Pan Pacific Connective Tissues Symposium
We were attending the 9th Pan Pacific Connective Tissue Societies Symposium and presenting some exciting new work.
“The Xbp1 arm of the UPR is triggered by the expression of mutant matrilin-3 (Matn3) and type X collagen (Col10a1), but only has a pro-survival role in a mouse model of Matn3-MED and not Col10a1-MCDS” as a POSTER presentation.
UK Strategy for rare Diseases – November 2013
The full document can be downloaded here: uk_strategy_for_rare_diseases
The launch of the SYBIL project
SYBIL (Systems biology for the functional validation of genetic determinants of skeletal diseases) project, a five year project funded by the European Commission. The overall concept of this large-scale collaborative project is to functionally validate genetic determinants of common and rare skeletal diseases to gain a mechanistic understanding of disease processes and age-related changes and to deliver new and validated therapeutic targets. SYBIL brings together a complementary translational and transnational group of world-class scientists, systems biologists, disease modellers, information technologists and industrialists that will achieve critical mass to deliver the ambitious objectives of this programme of research.
Skeletal diseases range from a large and diverse group of rare monogenic diseases (such as chondrodysplasias) to highly prevalent but genetically complex diseases such as osteoarthritis (OA) and osteoporosis (OP). The overall concept of this FP7-funded project is to study the genetic causes of both rare and common skeletal diseases in order to gain a better understanding of the disease processes and age-related changes. This fundamental research will help to deliver new and validated therapeutic targets that will eventually stimulate new therapies for these debilitating diseases.
SYBIL brings together a complementary group of world-class scientists, disease modellers, information technologists and industrialists that will deliver the ambitious objectives of this programme of research.
Notes:
- Rare skeletal diseases (RSDs) are an extremely diverse and complex group of diseases that primarily affect the development skeleton. There are more than 450 unique and well-characterised phenotypes that range in severity from relatively mild to severe and lethal forms. Although individually rare, as a group of related orphan diseases, RSDs have an overall prevalence of at least 1 per 4,000 children, which extrapolates to a minimum of 225,000 people in the 27 member states and candidate countries of the EU.
- OA is the most common form of arthritis and the World Health Organisation estimates that 25% of adults aged over 65 years suffer from pain and/or disability from OA and it is ranked 12th for disease burden in the EU25 and 35-40 million people suffer from OA in Europe. OA is estimated to be 30-70% genetic with strong environmental risk factors of ageing, obesity and joint trauma.
- OP is also a polygenic disease in which the quality and density of bones is reduced leading to weakness and increased risk of fractures. OP and its associated fractures are a major cause of morbidity and mortality since the lifetime risk for osteoporotic fractures in women is 30-50% and in men is 15-30%.
- OA and OP have a rising prevalence with age and result in a loss of independence with a greatly reduced quality of life and represent a major healthcare burden of increasing scale in Europe with the projected expansion of the elderly population.
Osteoarthritis Research Day 16th October 203
This month, we are participating in the exciting Osteoarthritis Research Day organised at the Institute of Cellular Medicine by our SYBIL partners.
Full programme:
20th November 2013 – STEM event in Gateshead
On 20th November 2013 we are participating in the STEM event organised for the Gateshead A-Level science/maths students by Gateshead College. This event involves ~12 workshops prepared by scientists from Newcastle and Northumbria Universities as well as local businesses representing STEM-type careers, such as electrical engineering, software & games, sports science, etc. The IGM Public Engagement Committee will host a ‘Biomedical Science’ workshop of 45 minutes repeated 5 times during the day to different students (~8-10 per workshop).
Jon Ingledew (Muscle team), Stephen Lisgo (HDBR) and Kasia Pirog (Skeletal group) are organising short hands-on activities to showcase the IGM research and allow the students to ask questions about the career in science in an informal setting.
If you would be interested in taking part in such events, please drop us an email at: IGMengagement@ncl.ac.uk
British Science Festival – 7th-12th September 2013
British Science Festival is coming to Newcastle 7th-12th September 2013!
Europe’s largest and longest running science event organised by the British Science Association, the Festival will be hosted by Newcastle University, in association with Northumbria University and Newcastle City Council.
With a fun packed programme of over 200 events across the city, the festival offers something for everyone, from a school student to a research scientist, giving people an opportunity to meet with the UK’s top scientists, engineers and industry. Public engagement committee at the IGM together with the School of English at Newcastle University are involved in the British Science Festival as well. We are organising a Young Science Writers Competition, to get the young minds interested and excited about the amazing field of DNA and genetics. The winning entries will be displayed at the Institute for Genetic Medicine for the duration of the British Science Festival and can be found on our website here.
Life Site Tours (British Science Festival 2013)
The IGM Public Engagement Committee, together with the Centre for Life and the NHS Fertility Clinic are hosting free site tours, offering a unique glimpse behind the scenes of the Centre for Life research labs and facilities as part of the British Science Festival 2013, on 7th and 8th of September 2013. The tours will include a chance to meet some of the people working at Life on the ground-breaking research.
The 
participants will have a chance to see behind the scenes of the famous Centre for Life, admire the view from the bridge link, take a peek inside one of our labs, see short presentations about the research done here at the IGM, visit the Newcastle Fertility Centre, and most importantly, meet the scientists!
Dr Carla Mellough from the stem cell group will talk about the exciting developments in heart and eye stem cell therapies, Dr Juliane Mueller will explain how zebrafish and mouse models can help in the research of muscular dystrophy, Harsh Sheth will talk about the exciting diagnostic technologies being developed by the Quantum Dx, Dr Simon Tual-Chalot and Esha Singh will talk about myocardial infarction and the novel therapies that are currently being developed at the IGM, Dr Steven Lisgo will display images generated by the MRC Wellcome Trust Human Developmental Biology Resource project (HDBR) and Dr Kasia Pirog will give an overview of the skeletal genetics research in the Institute. Jon Ingledew and Morten Ritso (Muscle Team) are coordinating the day and organising the display in the foyer.
Open Day for A-level students December 2012
On 5th December 2012 we are hosting an open day for A-level students from the schools around the North East. We invited 80 A-level students from 8 schools to have a look around the labs, learn a few techniques, hear exciting talks about the current research at the IGM and participate in the ethical debate about animal use in science. We are also running a workshop on University applications and an informal session with undergraduate representatives, to give the students a bit of a flavour of what life at Newcastle university may be like and what it has to offer.
We got a mention in the React magazine where you can read more about this event: http://reactmagazine.co.uk/anybody-out-there/public-engagement-school-kids-and-science/ and we will be organising more events of this kind in the future.We would like to thank all the people who volunteered to help with this event.