Prof Nowlan has been awarded seed funding together with Dr Sandra Shefelbine in Northeastern University, USA, to kick off an exciting new collaboration. Sandra and Niamh were colleagues and collaborators together at Imperial College London, and are very excited to be able to collaborate together again. The project is entitled “Mechanical Evaluation of Cartilage Hierarchy and Neo-Organisation” and will characterise the sequence of events by which the structure, composition and function of articular cartilage emerge over postnatal development.
Full details of the partnership scheme and the five funded projects are described here.
Prof Nowlan was awarded >€2 million through a prestigious ERC Consolidator Grant. The ‘ReZone’ project, aims to bring about enhanced regeneration of Articular Cartilage through activation of the developmental processes which form zonal functional cartilage in early life, and ultimately improve quality of life for patients with articular cartilage defects worldwide.
Professor Nowlan said: “I am thrilled and very grateful to be awarded an ERC Consolidator Grant. This will enable us to understand how mechanical loading affects the development of cartilage, with implications for both cartilage regeneration and for orthopaedic conditions affecting children. Articular cartilage is an amazing material that we depend upon for pain free movement. Due to its poor healing ability, cartilage needs to last a lifetime. What makes healthy cartilage low friction and long-lasting is its complex layered (zonal) structure, but current surgical techniques to fix damaged cartilage cannot recreate the original structure. Therefore, repair cartilage tends to break down, leading to the need for further surgeries and possibly even joint replacement.”
“In the ReZone project, we will find out how the zonal structure of cartilage forms after birth, and in particular how mechanical loading affects the cartilage layers. Through discovering how articular cartilage grows and develops, we hope to be able to (re)activate those processes in adults to be able to truly regenerate articular cartilage and help patients suffering from joint pain across the world. I would like to thank all of the people who helped in the preparation of the proposal, and all my collaborators. In particular I would like to acknowledge my key collaborator Professor Pieter Brama with whom I am excited to continue working closely. I would also like to acknowledge my funding sources to date in UCD, especially Science Foundation Ireland and Wellcome Leap”.
A paper entitled “Multi-modal detection of fetal movements using a wearable monitor” led by Dr Abhishek Ghosh (a former PhD student at Imperial College London, jointly supervised by Prof Nowlan) has been published in Information Fusion.
In the paper, we describe how a prototype wearable fetal movement monitor with multiple different types of vibration sensor was capable of detecting an impressive 82% of maternally sensed fetal movements with an overall accuracy of 90%. The excellent performance of the device was enabled in part by machine learning methods applied to the signals from the different sensors. For more details, please see the open-access paper here.
Congratulations to Abhishek and to all co-authors! Abhishek and Prof Nowlan continue to collaborate through their Wellcome Leap funded project to develop a wearable fetal movement monitor.
Congratulations to Saima whose paper was published in Royal Society Open Science. In the paper, we investigate how mechanical loading from fetal movements affects emergence and maturation of the different types of collagen in the developing skeleton. We found that most collagens were affected by the lack of muscle loading, with collagens II, X and XI being particularly abnormal when skeletal muscle was absent. Using our in vitro bioreactor culture system, we demonstrated that mechanical loading directly modulates the spatial localization and structure of collagens II and X, and excitingly, that mechanical loading in vitro could rescue aspects of the development of collagens II and X from the effects of fetal immobility.
Saima’s imaging is really beautiful- check out the full paper which is available open access here.
Congratulations to PhD Student Hannah Kane who won “Best Poster” prize at the 46th Research Students’ Conference in Probability and Statistics (RSC 2023) held in Sheffield, UK, on the 11-14th September 2023. Hannah’s poster was entitled “Novel insights gathered into the detailed analysis of the modified Waldenström classification”. Well done Hannah!
Funding worth in excess of €1.25 million from Science Foundation Ireland was announced for the project led by Prof Nowlan and Prof Brama was announced by Minister Simon Harris. The project entitled “Developmentally inspired approaches to cartilage defect healing” will be conducted over five years.
When injury to adult articular cartilage occurs, the defects do not heal, increasing the risk of joint disease and subsequent pain and suffering in humans and animals. In contrast, defects in immature cartilage can heal spontaneously, but there is little understanding of why only immature cartilage heals. Our aim is to recapitulate what happens in immature cartilage to heal adult cartilage defects. We will study which defects heal, and how, depending on animal age. We will use this knowledge to develop novel, ground-breaking treatments for cartilage repair in adult animals and humans.
Huge congratulations to Dr Yuming Huang who was conferred with his doctoral degree in the Royal Albert Hall in London on the 3rd May 2023. Niamh was delighted to be there for the lovely ceremony and to celebrate Yuming’s achievements.
Many congratulations to Jo and James who both passed their PhD vivas with minor corrections! 🤩 Thank you to all the examiners (Dr Kyra Campbell, Dr Choon Hwai Yap, Dr Prof Darryl Overby & Prof Sarah Waters) for their sterling efforts in putting Jo and James through their paces. Thank you too to former group members who rejoined us for the celebrations 🥳
James, Yuming and Niamh, together with alumni Nidal, Rebecca and Stefaan attended the 2023 Annual Meeting of the ORS in Dallas, Texas. James presented a poster, and Yuming and Niamh presented podium talks. Ireland was well represented as the 2023 Guest Nation!
James presenting his posterYuming’s podium presentationSome of the Irish representatives as part of the Guest Nation. Photo credit @LaoiseMcnamara
Nidal’s paper entitled “Mechanoregulatory role of TRPV4 in prenatal skeletal development” was published in leading journal Science Advances! The project was a fantastic team effort from Nidal, James, Yuming and Saima, together with collaborator in Trinity College Dublin David Hoey. This work was supported by European Research Council under the European Union’s Seventh Framework Program, ERC Grant agreement number 336306
The movements of a baby in the womb (fetal movements) are a critical sign of the baby’s health and development. Such movements are also important for development of the baby’s bones and joints. When a baby doesn’t move enough, or their movements are restricted in some way, the shapes of their joints don’t form correctly, leading to conditions such as developmental dysplasia of the hip (where the hip joint is unstable or dislocated) or arthrogryposis, where multiple joints are angled abnormally. There is a link between the mechanical forces caused by fetal movements and the processes by which the skeleton takes its shape, but the mechanisms underlying this relationship are unknown.
In this paper, we found that a particular ion channel called TRPV4 (transient receptor potential cation channel subfamily V member 4) is involved in the response of the growing skeleton to the mechanical forces caused by fetal movements. We discovered this link by blocking activity of TRPV4 in embryonic mouse limbs, and showing that the normal response of the tissues to mechanical loading was eliminated. We also showed that activation of TRPV4 by mechanical loading affects proliferation of cells and the production of matrix in the cartilage, both of which affect growth of the joint.
A fascinating thing about TRPV4 is that when the gene which codes for the TRPV4 protein is mutated, a range of different severe skeletal conditions can occur including lethal metatropic dysplasia, spondylometaphyseal dysplasia (dwarfism), and autosomal dominant brachyolmia. Our study is the first to demonstrate that TRPV4 activity in the developing skeleton is closely linked to the mechanical loading from fetal movements. Drugs aimed at targeting TRPV4 are being trialled for a range of different conditions including osteoarthritis and heart failure, and we believe that our research indicates that TRPV4 may be a valuable target for future therapeutic disease modifying drugs for abnormalities of paediatric skeletal development, particularly when fetal movements are reduced or restricted.
The paper was featured on the Science Advances homepage! Many congratulations to Nidal and all co-authors.
Developmental Biomechanics 