Programmed cell death is a physiological process through which unwanted cells are removed from organisms. During the development of the nematode C. elegans, 131 cells reproducibly die through programmed cell death, and this makes C. elegans an ideal model to study function, mechanism and regulation of programmed cell death across scales, from the organismal to the single cell level.
Most of the 131 cells that die during C. elegans development succumb through what is referred to as ‘apoptotic’ cell death, which depends on a conserved genetic pathway and culminates in the activation of a class of proteases called ‘caspases’. Recently, we discovered that the decision whether a cell lives or dies during C. elegans development is often made during the cell division that gives rise to that cell. Furthermore, we found that the conserved apoptotic pathway not only kills cells once they have been generated but actively participates in the ‘asymmetric’ cell divisions that give rise to these cells. Our future goal is to investigate changes in gene expression and cellular constituents, such as mitochondria, that are critical for these live versus death decisions and to elucidate the role of the apoptotic pathway in the decision making process.
The regulated transport of small molecules across biological membranes is essential for the establishment and maintenance of cellular sub-compartments that differ in terms of pH, metal ion concentrations, and metabolite pools. Thus, mutation of a gene that encodes a transporter protein often leads to pleiotropic defects in cell function, if not outright cell death. We are using C. elegans as a model system to study the function and regulation of evolutionarily-conserved P-type transporter proteins. In humans, mutations in these genes lead to neurodegenerative disease, whereas in nematodes we have characterized phenotypic signatures associated with defects in specific transporter proteins. For example, we have recently discovered that mutations in the P5B ATPases lead to defects in polyamine homeostasis. We are currently developing optogenetic tools that we can use to study the function and regulation of P5B ATPases at subcellular resolution within living animals.