Research

The control of growth

Our lab studies the control of growth using Drosophila as a model system. We use a combination of molecular and genetic approaches to investigate the cell-cell signalling pathways and the genetic mechanisms that govern how cell, tissue and body growth are controlled. Our main focus to-date has been the insulin and TOR kinase pathways

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The insulin/PI3K and TOR kinase signalling pathways control growth.

The insulin and TOR pathways are conserved signaling cascades in animals. They function as a nutrient-sensing pathways, coupling dietary conditions to the control of cell and organismal metabolism. As such, insulin/TOR signaling plays an essential role in controlling animal growth and maintaining cellular and organismal homeostasis.

In animals a complex signal transduction network activates the insulin/TOR pathways in response to growth factors and nutrient availability. Many oncogenes and tumor suppressors are components of this network. As a consequence of this elevated TOR activity is a common feature of tumour cells and may contribute to deregulated cell growth in cancer. The TOR pathway has therefore emerged as a promising target for therapy. Although the signalling inputs to TOR are becoming clear, the outputs via which TOR drives cell growth are still not fully understood. TOR controls many metabolic processes, such as protein synthesis, nutrient import, glucose metabolism, autophagy, and gene transcription. Defining which targets are critical for TOR function in animals should provide insights into both normal and tumour cell growth.

The Drosophila insulin/TOR pathway

In a four day period, the Drosophila larva will increase in mass by almost  200-fold. This growth is dependent in large part on insulin and TOR signaling. We therefore use the Drosophila larvae as a model system in which to study how the insulin and TOR pathway drives cell, tissue and body growth.

larvae

Our current interest is in examining how the insulin and TOR pathways regulate growth through the control of protein synthesis:

How does nutrient/TOR signalling regulate rRNA synthesis and ribosome biogenesis, and how does this regulation control growth? (Ghosh et al 2014, Killip and Grewal 2012, Grewal et al 2007, Grewal et al, 2005)

How does nutrient/TOR signalling regulate tRNA synthesis, and how does this regulation contribute to mRNA translation and growth? (Grewal 2015, Rideout et al 2012, Marshall et al 2012)

How does nutrient/TOR signalling regulate mRNA translation? (Nagarajan and Grewal 2014)