Functional polarity in renal tubules
Epithelial tubes transport life-sustaining gases, nutrients and fluids, so playing crucial roles in many contexts including in the kidney, lung, mammary and salivary glands. But they do more than simply convey material to and fro – they also modify the material passing through, so underpinning many of the homeostatic functions in our body. The correct development of transporting epithelial tubes is therefore essential to life. Epithelial tubes often have a functional polarity along their proximo-distal (P-D) axis, with different segments carrying out distinct physiological activities. Currently our understanding of how P-D axes and segment-specific differentiation are regulated during organogenesis is limited to a few isolated examples.
Insect Malpighian or renal tubules are structurally simple, but functionally sophisticated, epithelial tubes functioning primarily in excretion and regulation of water and ion levels within the body. They have a distinct P-D axis with segment-specific expression of proteins such as ion channels, to allow tightly controlled secretion and reabsorption along their length. We are utilising the genetic manipulation and in vivo imaging for which Drosophila is ideally suited, to determine developmental mechanisms that pattern the P-D axis and to link this to segment-specific cell differentiation and physiological function. We anticipate insights we gain to be widely relevant for understanding the development of epithelial tubes.
As inspiration we will turn our attention to the mechanisms of P-D axis formation in organs such as the vertebrate limb where morphogen gradients establish domains along the limb’s length, or in fly appendages, where concentric circles of gene expression initially pattern 2-D epithelial discs, which then ‘telescope out’ to give a 3-D adult structure with a defined P-D axis. By comparing our findings with these existing examples we also aim to gain broader insight into the mechanisms and principles that pattern P-D axes during development.
Molecular and cellular physiology of a powerful water-conserving system in beetles
Beetle bums, buried kidneys and the art of drinking through your anus: Insects are able to live and thrive in some of the most inhospitable environments on earth, including extreme conditions such as the desert. To survive these conditions, many species possess a powerful water-conserving system called the cryptonephridial (or ‘buried kidney’) complex, which recovers water from the rectum and recycles it back to the body. This remarkable system even allows absorption of water from moist air entering through the anus, providing a novel physiological mechanism for water uptake.
The project, which we are carrying out in collaboration with Kenneth Halberg at the University of Copenhagen, will use the beetle species Tribolium and Tenebrio (the red flour and mealworm beetles) to identify key transport mechanisms that drive the movement of water through the system.
It is anticipated that the work will significantly broaden our understanding of one of the most powerful water-conserving systems known to nature, with the possibility that it will unmask ‘design principles’ that may offer inspiration to biomimicry engineers. Tenebrionid beetles are devastating agricultural pests of flour and other dry-store grain products. Because the cryptonephridial complex is central to the beetle’s ability to survive dry conditions, our study could also pave the way for the discovery of novel pest management strategies.
A cardiac stretch-activated ion channel
The heart senses and adapts to its own highly dynamic mechanical environment. This environment changes beat-by-beat, and over longer timescales due to altered physiology or as a consequence of disease. Failure to detect and adjust cardiac performance accordingly is associated with arrhythmias and sudden cardiac death. The mechanism for this adaptation is not known.
Our goal is to study the cellular and molecular basis of this mechanism using the Drosophila heart as a simple model. Our preliminary data suggests that stretch-activated mechanosensitive ion channels are key components. Building on this we will investigate the hypothesis that these channels provide a direct link to convert physical force (stretch of the cardiac tissue) into biochemical signal (ion flux), which in turn regulates heart physiology and function (contractility).