Lindsay MacDougall

My lab has a long-standing interest in lipid signals and a more recent interest in cilia which we study using a range of techniques using the fruit fly, Drosophila.

We are interested in signalling lipids, particularly those made by an enzyme called the Class II Pi3-kinase. These signalling lipids, called phosphoinositides or PIPs for short, are important in regulating cellular processes in development and in the adult. Abnormal levels, particularly increases in these PIPs have been linked to human diseases such as cancer, diabetes, autoimmune diseases, myopathies and neuropathies. PIPs and the enzymes that make and degrade them are conserved between humans and fruit flies (Drosophila). We use fruit flies to study PIPs as we can easily genetically alter fruit flies and hence change the levels of PIPs in cells using mutants, RNA-interference and over expression systems. We can also use fluorescent probes to visualise PIPs within cells and tissues. 

The Class II Pi3-kinase that we study makes two distinct PIP signals: PI3P and PI(3,4)P2, and we can use fluorescent probes to distinguish between the contributions of these two signals to Class II Pi3-kinase mediated processes. We are particularly interested in the PI(3,4)P2 signal whose roles are less well understood.  For example, we have previously shown that the Class II Pi3-kinase has a growth inhibitory role and we want to establish whether PI(3,4)P2 is required for growth suppression by the Class II Pi3-kinase in vivo.  

I also have an additional research interest in cilia. Cilia have sensory and signalling functions and may be motile as in the epithelia of mammalian lung cells or the flagella of male gametes (sperm cells) and parasite tails. They are linked to a range of human diseases called ciliopathies that often affect many tissues but particularly the lung and kidneys and can cause infertility. Primary sensory cilia project from the cell and have a different composition from the main body of the cell. This is established and maintained by a molecular gating mechanism at the base of the cilium that contains transition zone and transition fibre proteins. However, some cilia including male gametes are formed within the cell ie not as a separate compartment but exposed to the cytosol. These “cytosolic” cilia also express certain transition fibre proteins. We want to understand how these transition fibre proteins function in the very distinct compartmentalised and cytosolic cilia, in part by identifying the proteins that they interact with. The fruit fly Drosophila provides an excellent model system to study cilia as cilia are restricted to certain sensory neurons (primary compartmentalised cilia) and the sperm flagellum (cytosolic cilia) hence mutations that cause defects in cilia give rise to adult flies with locomotor defects and male infertility.