Lockie Lab research
About Dr Sarah Lockie
Dr. Sarah Lockie started her PhD at the University of Cincinnati, Ohio, USA under the supervision of Professor Matthias Tschöp, and completed it at Monash University under the supervision of Professor Brian Oldfield. Her PhD work focused on physiology of anti-obesity therapeutics, aiming to amplify the therapeutic effects while minimising side effects. Her post-doctoral years were spent in the lab of Associate Professor Zane Andrews, also at Monash University, examining how function of the hormone ghrelin is influenced by nutritional status. She now leads a research programme within the Monash BDI, focused on anorectic (appetite-reducing) brain circuits, still closely collaborating with Associate Professor Zane Andrews.
Dr Lockie’s research focus is on appetite regulation in both adaptive and pathological circumstances. The bulk of our current understanding of energy balance regulation comes from studying dysregulation in obesity. Much less is understood about how the systems fails in diseases of underweight. While much less prevalent than obesity, these diseases are debilitating and deadly. Using cancer cachexia, diet-induced obesity and chronic calorie restriction as models, we look at mechanisms for failure to regulate body weight and food intake, and how this failure tracks with changes in memory, mood-related behaviour and motivation.
1. Neural control of cancer cachexia in a mouse model of pancreatic ductal adenocarcinoma (PDAC)
Cancer cachexia is the progressive loss of body weight, accompanied by loss of appetite, which affects around 80% of cancer patients. Using a mouse model of cachexia, we use cutting edge genetic tools to manipulate brain circuitry to prevent or reverse disease outcomes. Specifically, we focus on behaviour and physiological measures such as improved mood-related behaviour, metabolic rate, and feeding.
2. Metabolic and behavioural function of GDF15, and its target neurons, the GFRAL neurons
GDF15 it is secreted from the cells of most cancers and causes anorexia/cachexia in mice. Its receptor, Glial cell line-derived neurotrophic factor (GDNF)-family receptor α-like (GFRAL), is expressed solely in the brain. The GFRAL receptor was discovered in 2017, and as yet very little is known about its function or the brain circuits the GFRAL-containing neurons connect into. This project looks at how increased GDF15 expression can drive pathology, specifically focused on mood and motivational outcomes.
3. Anatomical and functional mapping of GFRAL neurons
Current evidence suggests that the GFRAL-expressing cells connect into anorectic circuitry important for supressing feeding in the event of poisoning or illness. This circuitry is important, as it reduces exposure to potential toxins in the wild, but it is pathologically activated in cachexia. This project looks directly at GFRAL neuronal function, and will characterise the function and connectivity of these cells.
4. Defining reciprocal neural circuits that regulate appetite and memory
Caloric restriction and ghrelin both improve adult hippocampal neurogenesis and memory function. This may be through direct action in the hippocampus, or through a metabolic-sensing relay such as the hypothalamus. Conversely, loss of hippocampal function leads to dysregulated appetite. This project investigates the neural mechanisms underpinning the regulation of these processes.
Visit Dr Lockie's Monash research profile to see a full listing of current projects.
- Genetically modified mouse lines for controlling and identifying neuronal populations
- Viral transgene delivery systems to genetically modify mice
- Behavioural assays including homecage operant learning of cognitive and motivation tasks, anxiety- and depression-related tasks, and maze and recognition tasks to assess memory
- Neural circuit tracing
- Neural circuit function (opto and chemogenetics to turn neurons on or off)
- Neural population recording (Fibre Photometry)
- Metabolic Physiology, including brown adipose tissue temperature recording
- Metabolic phenotyping
- Cancer cachexia (PDAC or LLC)
- Chronic calorie restriction
- Obesity/metabolic syndrome
We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).
Cancer Cachexia projects: Dr Kelly Walton and Associate Professor Craig Harrison, Monash University
Memory and appetite projects: Jeff Davies, University of Swansea
Student research projects
The Lockie Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.
Please visit Supervisor Connect to explore the projects currently available in our Lab.