Washington University researcher, Jing Hughes, was imaging the cilia in mouse pancreatic beta cells with the aim of observing static cilia and motile cilia in clumps of cells called islets when she saw that the primary cilia moved, having large implications for the potential therapeutic routes for people with Type 1 diabetes.
Cilia are most known for their role in lining the lungs and helping move mucus out of the airways and into the stomach to kill pathogenic microorganisms. However, they are present on the surface of almost every cell type and take up a 9+2 microtubule formation which aids with their motility.
The cilia studied by Hughes were cilia lining the beta cells in the pancreas, with beta cells being unique in their function of storing and releasing insulin. The importance of this discovery by Hughes is that the cilia lining the pancreatic cells are not meant to move as a result of force being generated within the structures. Therefore, this active motion could have a crucial role in regulating insulin secretion as it suggests these cilia can respond to their environment, instead of only being moved by surrounding fluids.
This has opened new doors for people with Type 1 diabetes as their autoimmune disease targets and kills beta cells, and so a therapeutic route for these potentially insulin-regulating cilia is promising.
After analysis, it was understood that they were a ‘hybrid’ between primary and motile cilia which contained structural and molecular aspects of both. To further shock the scientific community, the microtubule formation of these cilia was not 9+2 as expected but had eight microtubule doublets and a central microtubule doublet or singlet.
This deviation from the expected rotation caused pushback from the scientific community, with doubt arising as accusations of a misunderstanding were thrown Hughes’ way.
Hughes and her team employed a range of techniques to continue investigating their discovery through the uses of immunofluorescence and genetic deletion.
They first used immunofluorescence microscopy to visualise the proteins on the live beta cells. They discovered that the hybrid cilia had motor proteins which are only present in the known motile cilia: the lungs, middle ear, and the respiratory tract.
Through targeted genetic deletion, they were able to knock out the motor proteins and the motion of the beta cells’ cilia ceased. Genetic deletion is used to detect relatively small deletions inside of a given gene, in this case the gene encoding motor proteins, and then adding a form of marker to observe the result. From this experimental method they could conclude the cilia weren’t moving passively from their environment and could potentially regulate the function of beta cells themselves.
Hughes and her team hope to encourage the extended scientific community to take on this project to uncover how these hybrid cilia use motor proteins to regulate motion, and to partake in work that will further reiterate the important functionality of the cilia’s motion in a live eukaryote model.
