Timothy Sargeant

Timothy Sargeant

Adelaide Medical School

Faculty of Health and Medical Sciences

Eligible to supervise Masters and PhD - email supervisor to discuss availability.

A/Prof Tim Sargeant
BBMedSc. (Human Genetics), Hons. 1st Class, PhD, Victoria University of Wellington (New Zealand)

Please find my socials in the contact tab below, or email me at SAHMRI: Tim.Sargeant@SAHMRI.com

Addressing the Lifespan-Healthspan Gap:
While the 20th century brought remarkable increases in lifespan, reducing the gap between lifespan and healthspan remains a significant challenge. In countries like Australia, the last decade of life is often dominated by age-related diseases. To close this gap, we must address the fundamental drivers of cellular ageing.

Autophagy and lysosomal activity are vital cellular processes that recycle damaged and unwanted material. These mechanisms are crucial for maintaining cellular health during ageing. When they are impaired, biological ageing accelerates, contributing to age-related diseases like atherosclerosis and dementia — leading causes of death in Australia.

A/Prof Tim Sargeant’s team has developed innovative tools to measure autophagy and lysosomal activity in humans and is working on therapies to enhance this recycling machinery. By targeting the biology of ageing itself, their research seeks to improve healthspan and provide transformative solutions to combat age-related diseases at their root.

Scientific Background and Research Focus:
A/Prof Tim Sargeant began his scientific journey with a PhD in neuroscience at Victoria University of Wellington, New Zealand. He subsequently undertook two postdoctoral fellowships at the University of Cambridge (UK), where he gained expertise in molecular and cell biology, focusing on the lysosomal system—the cell’s recycling machinery.

In 2015, Tim was appointed Head of Lysosomal Health in Ageing at the South Australian Health and Medical Research Institute (SAHMRI). His research investigates the role of the lysosomal system in biological ageing, with an emphasis on its ability to clear damaged and unwanted cellular material. By understanding how lysosomal recycling slows cellular ageing, Tim’s work addresses how this process underpins the prevention and treatment of age-related diseases.

Research Overview

Preclinical studies have established that autophagy is vital for healthy ageing, with enhanced autophagy promoting longer healthspans in disease models. However, our understanding of autophagy in humans remains limited. This gap presents a significant challenge for drug development, as pharmaceutical companies cannot readily measure autophagy activity in clinical trials, thereby hindering the translation of autophagy-enhancing drugs and interventions.

To address this critical issue, our research has focused on developing innovative approaches to measure autophagy and lysosomal function in humans. We currently have three active projects:

  1. Direct measurement of autophagy using human blood.
  2. Development of biomarkers for autophagy in human biofluids.
  3. Imaging lysosomal function using positron emission tomography (PET).

This research program has been supported by including but not limited to three NHMRC Ideas Grants and a BrightFocus grant (A/Prof Sargeant as lead investigator).

Direct Measurement of Autophagy Using Human Blood

Overview
The direct measurement of autophagic flux in whole human blood represents our most advanced autophagy assessment technology. This method captures critical data about autophagy within a physiologically intact environment, an essential factor as autophagy is highly sensitive to disruptions.

Methodology
Autophagic flux is measured by detecting LC3B-II through techniques such as western blot, flow cytometry, or ELISA, as illustrated in the accompanying figure.

Direct measurement of human blood autophagy

Milestones and Applications
Since its initial publication in 2021, this method has been adopted in studies by our research group and external collaborators.

Key Publications

  • Research from Lysosomal Health in Ageing (SAHMRI):
  • Collaborative research with Lysosomal Health in Ageing (SAHMRI):
  • Research from external groups:

Intellectual Property
This technology is protected by patent in the UK (GB2603664B), with patents pending in Australia and the United States.

Development of Biomarkers for Autophagy in Human Biofluids

Addressing a Critical Gap
Our autophagy biomarker programme focuses on discovering and validating blood-borne molecules indicative of intracellular autophagy. While not as mature as our direct autophagy blood test, this initiative is vital for advancing the field.

Strengths and Capabilities

  • Mechanistic Insights: Our team of world-class cell biologists investigates the mechanistic links between candidate biomarkers and autophagy, ensuring a deep understanding beyond simple correlations.
  • Integrated Approach: Collaborations with SAHMRI's Bioresources and Clinical Trials Platform enable us to validate candidate biomarkers in both preclinical models and human studies.

Impact
Validated biomarkers will enable clinic- or home-friendly autophagy measurements, a key step in translating fundamental ageing science into practical applications.

Imaging Lysosomal Function Using Positron Emission Tomography (PET)

Expanding the Toolkit
While biofluid-based tests are crucial for assessing autophagy, imaging the lysosomal system directly within tissues offers unique insights. This programme aims to develop PET imaging technologies to predict disease emergence, such as the hallmarks of Alzheimer’s disease in the brain.

Current Status
This initiative is in its early stages and is being conducted in collaboration with the Molecular Imaging and Therapy Research Unit (MITRU) at SAHMRI.

Future Vision
Advanced imaging technologies will provide a transformative approach to understanding lysosomal health and predicting disease at the tissue level.

  • Appointments
    Date Position Institution name
    2024 - ongoing Associate Professor (Affiliate) University of Adelaide

  • Education
    Date Institution name Country Title
    Victoria University of Wellington New Zealand PhD

We have received funding from the following organisations:

NHMRC

BrightFocus

Diabetes Australia

The Rebecca L Cooper Medical Research Foundation

I teach in the following courses at the University of Adelaide:

Bachelor of Medical Studies (Medical Studies 3) - Ageing 1: Cellular Mechanisms and Ageing 9: Neurological Ageing (2023 - present)

PSYCHIAT 3200 (Fundamentals of Biological Psychiatry) - Biological mechanisms that underpin Alzheimer’s disease (2022 - present)

Biochemistry III (Cancer, Stem Cells and Development) - mTOR, autophagy and cancer (2018- present)

  • Current Higher Degree by Research Supervision (University of Adelaide)
    Date Role Research Topic Program Degree Type Student Load Student Name
    2023 Principal Supervisor Lysosomal function in cellular senescence Doctor of Philosophy Doctorate Full Time Dr Hourieh Tousianshandiz

  • Past Higher Degree by Research Supervision (University of Adelaide)
    Date Role Research Topic Program Degree Type Student Load Student Name
    2019 - 2024 Principal Supervisor Beyond LC3-associated phagocytosis: cross-talk between autophagy and efferocytosis during microglial corpse clearance Doctor of Philosophy Doctorate Full Time Miss Sanjna Singh
    2018 - 2023 Co-Supervisor Investigation of the Endolysosomal Network in A Drosophila Model of Alzheimer’s Disease Doctor of Philosophy Doctorate Full Time Miss Sher Li Tan
    2015 - 2020 Co-Supervisor The Role of Heterozygous Lysosomal Storage Disorder Alleles as Risk Factors for Dementia Doctor of Philosophy Doctorate Full Time Ms Lauren Sue Whyte

  • Committee Memberships
    Date Role Committee Institution Country
    2025 - ongoing Chair Institutional Biosafety Committee SAHMRI Australia
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