Our laboratory studies how molecules and organelles traffic within cells, with a particular emphasis on the motility and function of lipid droplets. Lipid droplets are fat storage organelles that play crucial roles in cellular and organismal lipid homeostasis, but also have many additional roles in the cell that are just being discovered. We focus on two of those roles: lipid droplets can serve as storage sites for proteins from other cellular compartments (Welte, 2007),
Lipid droplets (yellow) in early Drosophila embryos. Droplet distribution is controlled by active transport along microtubules. and lipid droplets move actively along microtubules, using the motors kinesin-1 and cytoplasmic dynein (Welte, 2009)
To understand how and why lipid droplets sequester proteins and how and why lipid droplets move, we are studying Drosophila embryos; these embryos are full of highly motile lipid droplets (Welte et al., 1998) and can easily be manipulated (Tran and Welte, 2010). This model system allows us to employ an interdisciplinary approach, applying tools from genetics, imaging, molecular biology, biophysics, and biochemistry. Using this system, we have discovered that lipid droplets can store histones to support embryonic development (Li et al., 2013) and that how microtubule motors are regulated in vivo is very different from their behavior in vitro (Shubeita et al, 2008).
Kinesin-1 and cytoplasmic dynein work together to transport many intracellular structures besides lipid droplets, from RNA particles to mitochondria to entire nuclei (see Welte, 2004). How such bidirectional transport is controlled by the cell is only incompletely understood. In Drosophila, the nesprin ortholog Klarsicht modulates a wide range of transport processes (discussed in Kim et al., 2013), likely by controlling the activites of kinesin-1 and/or dynein. We are dissecting the mechanism by which Klarsicht acts, with particular emphasis on RNA transport during oogenesis.
For more details on our projects, please check out the links below:
- Lipid droplets as protein sequestration sites
- Temporal regulation of lipid-droplet motion
- Control of intracellular transport by the Klarsicht protein