There’s so much yet to be understood about the cells that make up our own bodies. Martin Knight talks us through one aspect of them, the Primary cilia, where potentially life changing discoveries are being made.
Martin is a Professor of Mechanobiology and bioengineer based at Queen Mary University of London. His research examines how living cells and tissues within our bodies ‘sense and respond’ to mechanical forces. Outside work, Martin enjoys the ‘great outdoors’ and has had many enjoyable expeditions to wilderness areas.
Our bodies are made up of millions of cells. There are tiny, hair-like structures on the majority of these cells, each of which is called a cilium, or cilia, in the plural. The structure of cilia is similar to that of flagella, structures that form the tails of sperm and other specialist cells, enabling them to swim. There are two main types of cilia, namely: motile cilia or flagella and primary cilia. Motile cilia were first identified in 1675 by tradesman and scientist Anthony van Leeuwenhoekin, who was later recognised as ‘the father of Microbiology’. Although cilia are among the oldest known cellular features, we are only just beginning to understand the importance of primary cilia in health and disease. Scientists believe that these specialised structures may hold the key to exciting new treatments for diseases such as arthritis, osteoporosis, cardiovascular disease, and cancer.
Some cell types, such as those lining our airways, are covered in motile cilia. The motile cilia on these cells all beat in unison, pushing fluid over the surface of the cell. This movement helps to move mucus and keep our lungs clean. Primary cilia, on the other hand, lack the molecular motors needed to actively move or ‘beat’. They also only exist as one primary cilium per cell. Primary cilia are present in the majority of cell types in our tissues, including bone, cartilage, skin, blood vessel, nerves and even stem cells.
Although primary cilia are present in a widespread number of cell types compared to motile cilia, we have only recently begun to understand their function through the identification of a group of rare genetic diseases, collectively known as ciliopathies. These abnormalities occur when the genes that control the structure and function of primary cilia are mutated. The most common form of ciliopathy is polycystic kidney disease, in which a dysfunction of cilia in the kidney leads to the formation of large cysts which disrupt kidney function. By studying these diseases, we have discovered that primary cilia are important in coordinating a number of cellular functions and signalling pathways, which are crucial in the development and health of our tissues.
One important function of the primary cilia is to regulate a cell’s response to the mechanical forces to which are tissues are routinely exposed. For example in the kidney or blood vessels, this involves shear forces caused by the flow of fluid, where as in cartilage in our joints, the tissue and the cells are exposed to compressive forces. Nineteenth century German anatomist and surgeon, Julius Wolff, found that the more mechanical force is applied to a bone, the more densely the bone develops. On the other hand, if the bones are subjected to less mechanical force, or reduced loading, a process known as ‘bone resorption’ occurs, in which the bone tissue is slowly resorbed. This explains the increased bone density in the racket hand of a professional tennis player and the reduced bone density in the legs of a person with paralysis.
We now know that this critical response to mechanical force is coordinated by primary cilia in a variety of cells and tissue types. In the kidneys, for example, the primary cilia on the cells that line the tubules, project out into the lumen through which the urine flows. The cilia on these cells are thought to sense the flow of urine by the way they bend, activating specialised receptors on the surface of the cilium. However, the mechanism by which primary cilia regulate how cells sense and respond to mechanical forces in other cell types is still unclear. For example, in cells where cilia don’t project out from the cell or where the cilia are completed embedded in the tissue, such as the articular cartilage that cover the ends of bones in our joints. In these tissues, primary cilia are unlikely to deflect or bend in response to mechanical forces. And yet recent studies clearly show that primary cilia are essential for these cells to be able to respond correctly to to mechanical forces. So how do they do it? The answer is: we still don’t know. Scientists are currently trying to understand exactly how primary cilia regulate the fundamental ability of a cell to detect and respond to mechanical forces which is so important for the development and health of our tissues.
Recent studies have also found that other physical or chemical stimuli can regulate the structure of primary cilia, leading to functional alterations in cell behaviour. Apart from regulating the response to mechanical forces, primary cilia also coordinate other aspects of cell function, such as differentiation of stem cells, the response to inflammation and the correct development of tissue as we grow. Interestingly, inflammation and tissue development are important components of diseases such as cancer, cardiovascular disease and osteoarthritis, all of which may be associated with changes in the structure and function of primary cilia. This has prompted scientists to question whether changes in cilia structure regulate the progression of these diseases. Could this be a clue in our search for cures?
Scientists are now beginning to realise that several widespread diseases are associated with the disruption of primary cilia structure and function caused by physical or chemical alterations in the cellular environment. This idea of ‘environmental’ as opposed to genetic ciliopathies leads to the exciting possibility that we may be able to develop drugs that manipulate primary cilia as part of a new class of treatment, termed ciliotherapy. For example, Professor Martin Knight, a bioengineer at Queen Mary University of London, is working on exploring the potential of ciliotherapy for the treatment of osteoarthritis. This painful and debilitating condition affects over 8 million people in the UK alone, and currently has no known cure. Interesting new studies suggest that this condition is influenced by changes in primary cilia structure and function. Drugs which regulate cilia may therefore hold the key to treating osteoarthritis.
To really unlock the potential of ciliotherapy, for treatment of osteoarthritis and other diseases , it is essential to properly understand the role of this amazing and hitherto largely ignored, cellular structure: the primary cilium.
by Oscar Williams
How can the behaviour of a single atom provide insights into our energy demands? How do we know that atoms actually exist? And what on Earth do the acronyms XPS, STM and UHV stand for? If you find yourself wondering ...
by Simon Schoeller
I’m an academic who spends a lot of time studying sperm, and sperm’s collective behaviour. The twist? I’m a not a biologist, I’m a mathematician.
To many scientists, how tiny cells and organisms manage to swim is a fascinating topic ...