Johnson - Mechanisms of cell signalling regulation, treatments for rare genetic disorders
The Johnson group investigates the complex interplay between cells and their environment to better understand the molecular processes that underpin animal development and health. Travis’ interests span from the molecular scale, understanding how proteins control cell-to-cell communication, through to body tissues and whole organism scales looking at physiology in the disease state. This is made possible because his team uses the fruit fly Drosophila melanogaster as an animal model. Flies have a fast lifecycle, can be easily manipulated at the genetic level, and have many similarities with humans, from their genes to entire body systems. The broad objective is to use Drosophila as a biomedical research tool to reveal new mechanisms of cell signalling control, as well as learn how disease affects the body for the development of targeted, precision nutrition and drug therapies.
Research areas
Modelling inherited metabolic disorders
There are more than 1,000 inherited metabolic disorders (IMDs) known which collectively affect approximately 1 in 800 births. Tragically, IMD often cause rapid neurological decline and death during infancy, and due to their rarity and large overall number, IMD remain a major challenge for treatment development. Our Group is addressing this by generating fly models of IMDs to understand these diseases and find new treatments.
We are approaching IMD treatment discovery in two different ways: Firstly, IMDs are unique amongst inherited disorders because they are often very responsive to dietary changes owing to their metabolic basis. As part of our work, we have developed a fully customizable synthetic diet for Drosophila so that we can systematically screen our fly IMD models across a large number of nutrient-varied diets to find those that restore their health.
Secondly, we are developing a high-throughput drug trial pipeline for Drosophila which we will use to identify compounds with clinical potential for treating rare genetic diseases. With these approaches and unique capabilities, our goal is to translate our findings to mammalian models and into the clinic to reduce the suffering of those with IMDs.
Control of the blood cell population size
Our work on cell signalling control has led us to study the macrophage: a highly versatile blood cell responsible for a plethora of activities that support animal health. Despite having been studied for more than a century, we still know very little about how their numbers and distribution around the body are controlled. In Drosophila, more than 95% of the blood cells are macrophages, making them ideal for such studies. We have developed a suite of sophisticated genetic and imaging tools for their study. We currently have a number of projects focused on macrophage biology including: identifying cell signalling pathways that control macrophage number, and applying new approaches to study their response to environmental and genetic perturbations.
Mechanisms of cell signalling
A major focus of our research concerns how cells communicate at the earliest stages of animal development - the embryo. Here we study a receptor pathway that is activated in a unique spatial manner for a critical developmental process, the control mechanism of which is poorly understood. We are applying biochemical and structural biology approaches in concert with in vivo developmental biology techniques to reveal how signalling is controlled at the molecular level. Interestingly, a key player in this mechanism is related to bacterial toxins and vertebrate immunity effectors usually associated with cell-killing. Unravelling how such a molecule functions in the early embryo to control receptor activity may therefore shed light on several areas of biology, as well as have implications in the development of therapeutics for developmental disorders and cancer, where cell signalling is dysregulated or hijacked.
