Whether its in you, a blue whale or a tiny insect, circulating fluids bathe and nourish organs, tissues and cells. To avoid compromising organ function, these ‘bloods’ are filtered and kept free of unwanted molecules. Studying these clearance mechanisms informs us about normal physiology, as well as disease across a vast array of organisms, from flies to humans.
In a new paper led by BU, it has been established that a mechanism common to flies and humans involving a protein called Amnionless, relies on a cell’s calcium level being controlled by genes known as Stim and Orai. Using powerful fruit fly genetics and dynamic cellular imaging techniques, the researchers found that as calcium levels change, Amnionless is turned-over at the cell surface where is helps to remove unwanted molecules. This new information is important because of its relevance to the human kidney’s role in blood filtration. Additionally, research is showing that the mechanism can be targeted by environmental toxins and this may explain why some insect species are struggling in the wild.
It is sobering to think that aspects of human cardiovascular disease and the ‘insect apocalypse’ may actually have common origins. Understanding these biological systems therefore has a dual purpose by informing medical, biomedical and ecological research fields.
(The image shows insect filtration cells in blue, adjacent to the heart, coloured magenta).
Every beat of the heart is finely tuned to eject a certain amount of blood. As we exercise, more blood flows into the heart, the cardiac muscle stretches and this leads to an increased force of contraction. Known as the Frank-Starling law, it is one of the most important aspects of human cardiac physiology but the molecular mechanisms are not entirely understood.
We do know that increases to the calcium levels in the heart cells (cardiomyocytes) support stronger contractions (anyone remember the ‘sliding ratchet model’ from GCSE biology!?) but how this calcium is regulated by stretch is not fully understood. What my colleagues and I have established (to be published in Frontiers of Physiology) is that a ‘mechanosensitive’ protein known as Piezo helps increase calcium when the cardiomyocytes are stretched. A lot of this work was done at BU’s Drosophila (fruit fly) genetics facility in Dorset House, using physiological tests of heart function in flies without the Piezo protein. When stretched, normal hearts respond by releasing more calcium and they continue to beat. In Piezo mutants, there’s no increase in calcium and the hearts often stop beating.
This is an important observation that contributes to our fundamental understanding of cardiac physiology and points to Piezo as a protein of considerable interest when considering the underlying causes of cardiac dysfunction in disease and ageing.
(The image shows the contractile protein ‘scaffold’ within an insect heart)
MRC are opening up a £2,000,000 fund on 6th May for improving the methods used by others in biomedical and health research.
Deadline: 15th June 2022
The full economic cost of your project can be up to £625,000. MRC and NIHR will fund 80% of the full economic cost.
This is an ongoing scheme. Application rounds open twice per year, closing in June and November
More details on the funding opportunity here.
Your local branch of the NIHR RDS (Research Design Service) is based within the BU Clinical Research Unit (BUCRU)
We can help with your application. We advise on all aspects of developing an application and can review application drafts as well as put them to a mock funding panel (run by RDS South West) known as Project Review Committee, which is a fantastic opportunity for researchers to obtain a critical review of a proposed grant application before this is sent to a funding body.
Contact us as early as possible to benefit fully from the advice
Feel free to call us on 01202 961939 or send us an email.