Timothy Sargeant
Adelaide Medical School
Faculty of Health and Medical Sciences
Eligible to supervise Masters and PhD - email supervisor to discuss availability.
Dr Tim Sargeant BBMedSc. (Human genetics), Hons. 1st Class, Victoria University of Wellington (New Zealand), PhD, Victoria University of Wellington (New Zealand) - TITLEHOLDER.
Twitter: @timsargeant1
ResearchGate: https://www.researchgate.net/profile/Timothy-Sargeant
Dr Tim Sargeant started his career in neuroscience with a PhD at Victoria University of Wellington, New Zealand. Tim went on to two postdoctoral positions at the Department of Medicine and the Department of Pathology at the University of Cambridge (UK) where he researched the cell’s recycling machinery (called the lysosomal system) and obtained training in molecular and cell biology. Tim was appointed to head of Lysosomal Health in Ageing in the Hopwood Centre for Neurobiology (formally the Lysosomal Diseases Research Unit) at SAHMRI in 2015. His current research focuses on the role of lysosomal recycling in common age-related disease such as Alzheimer’s disease.
The lysosomal system is important for slowing cell ageing, as it removes damaged and unwanted material from the cell. This process is critically important for healthy brain function. Work from Lysosomal Health in Ageing has shown that this system is damaged in Alzheimer’s disease, and that changes in genes that are involved in the lysosomal system are associated with Alzheimer’s disease. Our current research focuses on development of methods for measurement of lysosomal system activity (through a process called autophagy) in humans. We are also developing interventions that improve the lysosomal system with the goal of delaying Alzheimer’s disease.
Current student positions available (Honours/Masters/PhD available):
Group: Lysosomal Health in Ageing, Lifelong Health Theme, SAHMRI
Contact: Dr Tim Sargeant, Tim.Sargeant@SAHMRI.com, please add “STUDENT PROJECT” to the subject line
Project: “Reduced protein intake counteracts Alzheimer’s disease: examination of nutrition signaling and the lysosomal system.”
Alzheimer’s disease (AD) leads to the progressive formation and spread of what are termed ‘plaques’ in the brain, which impair its function and cause dementia. When we are young, our brain can efficiently clear plaque-related material and prevent it from building up. However, starting from middle age, this clearance system (called ‘autophagy’) works less efficiently and plaques can start to accumulate and spread. Our group has found autophagy can destroy the material that contributes to plaques and that we can activate autophagy using drugs or restricting certain nutrients in the diet. These nutrients include amino acids (the building blocks of protein), which help to suppress the rate of clearance. As a part of a larger study, we are looking for a student to determine the effect of dietary protein on prevention of amyloid plaque formation in the brain. The student will also use laboratory models to determine whether this dietary intervention works through autophagy. At the end of the project, the student will be proficient in applying dietary interventions to laboratory models, behavioural measurements, and assessment of Alzheimer’s disease-related pathology. We will consider Honours, Masters, or PhD students for this project.
Group: Lysosomal Health in Ageing, Lifelong Health Theme, SAHMRI
Contact: Dr Tim Sargeant, Tim.Sargeant@SAHMRI.com, please add “STUDENT PROJECT” to the subject line
Project: “The molecular basis of healthy ageing: exploring the intersection between ageing, obesity, and autophagy.”
Autophagy actively repairs cell damage driven by ageing, obesity, and chronic inflammation, which are all highly related biological processes. Preclinical studies have shown that inefficient autophagic function contributes to development of age-related diseases, including cardiovascular disease and dementia. We hypothesise that individuals who cannot aggressively upregulate autophagy in response to ageing will be at a higher risk of developing age-related disease. This project will test this hypothesis by determining how autophagy changes in multiple different tissues (including leukocytes, heart, and brain tissues) using autophagy reporter tf-LC3 transgenic laboratory models. The student will also assess whether decreased autophagy increases age- and obesity-related cell damage, inflammation, and cognitive decline in autophagy-deficient Becn1+/- laboratory models. It is highly likely that changes in autophagic function mechanistically link ageing and obesity with major age-related diseases in humans. Determining the extent of this relationship will eventually help to identify people with a higher disease risk that would benefit from autophagy-augmenting interventions. At the successful completion of this project, the student will be proficient in dietary interventions with laboratory models, behavioural measurement, and the use of transgenic laboratory models to investigate age-related cell biology. We will consider Honours, Masters, or PhD students for this project.
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Journals
Year Citation 2024 Singh, S., Bensalem, J., Hein, L. K., Casey, A., Mäkinen, V. -P., & Sargeant, T. J. (2024). epHero - a tandem-fluorescent probe to track the fate of apoptotic cells during efferocytosis.. Cell death discovery, 10(1), 179.
2023 Sargeant, T. J., & Fourrier, C. (2023). Human monocyte-derived microglia-like cell models: A review of the benefits, limitations and recommendations. Brain, Behavior, and Immunity, 107, 98-109.
Scopus5 WoS1 Europe PMC32023 Carosi, J. M., & Sargeant, T. J. (2023). Rapamycin and Alzheimer disease: a hypothesis for the effective use of rapamycin for treatment of neurodegenerative disease. Autophagy, 19(8), 2386-2390.
Scopus6 WoS1 Europe PMC52023 Bensalem, J., Hein, L. K., Hassiotis, S., Trim, P. J., Proud, C. G., Heilbronn, L. K., & Sargeant, T. J. (2023). Modifying Dietary Protein Impacts mTOR Signaling and Brain Deposition of Amyloid β in a Knock-In Mouse Model of Alzheimer Disease. Journal of Nutrition, 153(5), 1407-1419.
Scopus12023 Schwarz, N., Fernando, S., Chen, Y. -C., Salagaras, T., Rao, S. R., Liyanage, S., . . . Psaltis, P. J. (2023). Colchicine exerts anti-atherosclerotic and -plaque-stabilizing effects targeting foam cell formation. The FASEB Journal, 37(4), 1-20.
Scopus9 WoS2 Europe PMC42023 Teong, X. T., Liu, K., Vincent, A. D., Bensalem, J., Liu, B., Hattersley, K. J., . . . Heilbronn, L. K. (2023). Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial. Nature Medicine, 29(4), 963-972.
Scopus20 WoS8 Europe PMC92023 Carosi, J. M., Denton, D., Kumar, S., & Sargeant, T. J. (2023). Receptor Recycling by Retromer. Molecular and Cellular Biology, 43(7), 317-334.
Scopus4 Europe PMC22023 Bensalem, J., Teong, X. T., Hattersley, K. J., Hein, L. K., Fourrier, C., Liu, K., . . . Sargeant, T. J. (2023). Basal autophagic flux measured in blood correlates positively with age in adults at increased risk of type 2 diabetes. Geroscience, 45(6), 3549-3560.
Scopus1 WoS1 Europe PMC12023 Carosi, J. M., Hein, L. K., Sandow, J. J., Dang, L. V. P., Hattersley, K., Denton, D., . . . Sargeant, T. J. (2023). Autophagy captures the retromer-TBC1D5 complex to inhibit receptor recycling. Autophagy, 20 pages.
2022 Bensalem, J., Heilbronn, L. K., Gore, J. R., Hutchison, A. T., Sargeant, T. J., & Fourrier, C. (2022). The Break-Fast study protocol: a single arm pre-post study to measure the effect of a protein-rich breakfast on autophagic flux in fasting healthy individuals. BMC Nutrition, 8(1), 120-1-120-7.
2022 Casey, A. E., Liu, W., Hein, L. K., Sargeant, T. J., Pederson, S. M., & Mäkinen, V. P. (2022). Transcriptional targets of senataxin and E2 promoter binding factors are associated with neuro-degenerative pathways during increased autophagic flux. Scientific Reports, 12(1), 12 pages.
Scopus1 Europe PMC12022 Carosi, J. M., Fourrier, C., Bensalem, J., & Sargeant, T. J. (2022). The mTOR–lysosome axis at the centre of ageing. FEBS Open Bio, 12(4), 739-757.
Scopus31 WoS19 Europe PMC172022 Whyte, L. S., Fourrier, C., Hassiotis, S., Lau, A. A., Trim, P. J., Hein, L. K., . . . Sargeant, T. J. (2022). Lysosomal gene Hexb displays haploinsufficiency in a knock-in mouse model of Alzheimer's disease. IBRO Neuroscience Reports, 12, 131-141.
Scopus8 WoS6 Europe PMC72022 Casey, A., Liu, W., Hein, L., Sargeant, T., Pederson, S., & Mäkinen, V. -P. (2022). Transcriptional targets of senataxin and E2 promoter binding factors are associated with neuro-degenerative pathways during increased autophagic flux.
2022 Chaudhary, R., Liu, B., Bensalem, J., Sargeant, T. J., Page, A. J., Wittert, G. A., . . . Heilbronn, L. K. (2022). Intermittent fasting activates markers of autophagy in mouse liver, but not muscle from mouse or humans. Nutrition, 101, 1-7.
Scopus5 WoS2 Europe PMC52022 Vidanapathirana, A. K., Goyne, J. M., Williamson, A. E., Pullen, B. J., Chhay, P., Sandeman, L., . . . Bursill, C. A. (2022). Biological Sensing of Nitric Oxide in Macrophages and Atherosclerosis Using a Ruthenium-Based Sensor. Biomedicines, 10(8), 1807.
Scopus4 WoS2 Europe PMC12021 Shoubridge, A. P., Fourrier, C., Choo, J. M., Proud, C. G., Sargeant, T. J., & Rogers, G. B. (2021). Gut Microbiome Regulation of Autophagic Flux and Neurodegenerative Disease Risks. Frontiers in Microbiology, 12, 10 pages.
Scopus6 WoS6 Europe PMC62021 Carosi, J. M., Hein, L. K., van den Hurk, M., Adams, R., Milky, B., Singh, S., . . . Sargeant, T. J. (2021). Retromer regulates the lysosomal clearance of MAPT/tau. Autophagy, 17(9), 2217-2237.
Scopus16 WoS20 Europe PMC152021 Fourrier, C., Bryksin, V., Hattersley, K., Hein, L. K., Bensalem, J., & Sargeant, T. J. (2021). Comparison of chloroquine-like molecules for lysosomal inhibition and measurement of autophagic flux in the brain. Biochemical and Biophysical Research Communications, 534, 107-113.
Scopus5 WoS3 Europe PMC32021 Carosi, J. M., Denton, D., Kumar, S., & Sargeant, T. J. (2021). Retromer dysfunction at the nexus of tauopathies. Cell Death and Differentiation, 28(3), 884-889.
Scopus10 WoS9 Europe PMC72021 Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., . . . Aurelian, L. (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)<sup>1</sup>. Autophagy, 17(1), 1-382.
Scopus1303 WoS810 Europe PMC9702021 Xie, J., De Poi, S. P., Humphrey, S. J., Hein, L. K., Bruning, J. B., Pan, W., . . . Proud, C. G. (2021). TSC-insensitive Rheb mutations induce oncogenic transformation through a combination of constitutively active mTORC1 signalling and proteome remodelling. Cellular and Molecular Life Sciences, 78(8), 4035-4052.
Scopus5 WoS2 Europe PMC22021 Bensalem, J., Fourrier, C., Hein, L. K., Hassiotis, S., Proud, C. G., & Sargeant, T. J. (2021). Inhibiting mTOR activity using AZD2014 increases autophagy in the mouse cerebral cortex. Neuropharmacology, 190, 15 pages.
Scopus7 WoS6 Europe PMC22021 Hattersley, K. J., Carosi, J. M., Hein, L. K., Bensalem, J., & Sargeant, T. J. (2021). PICALM regulates cathepsin D processing and lysosomal function. Biochemical and Biophysical Research Communications, 570, 103-109.
Scopus4 WoS3 Europe PMC22021 Lynn, M. A., Eden, G., Ryan, F. J., Bensalem, J., Wang, X., Blake, S. J., . . . Lynn, D. J. (2021). The composition of the gut microbiota following early-life antibiotic exposure affects host health and longevity in later life. Cell Reports, 36(8), 20 pages.
Scopus29 WoS18 Europe PMC192021 Sargeant, T. J., & Bensalem, J. (2021). Human autophagy measurement: an underappreciated barrier to translation. Trends in Molecular Medicine, 27(12), 1091-1094.
Scopus5 WoS5 Europe PMC42021 Carosi, J. M., Nguyen, T. N., Lazarou, M., Kumar, S., & Sargeant, T. J. (2021). ATG8ylation of proteins: a way to cope with cell stress?. The Journal of Cell Biology, 220(11), 1-4.
Scopus7 WoS5 Europe PMC52020 Xie, J., De Poi, S., Humphrey, S., Hein, L., Bruning, J., Pan, W., . . . Proud, C. (2020). TSC-Insensitive Rheb Mutations Induce Oncogenic Transformation Through a Combination of Hyperactive mTORC1 Signalling and Metabolic Reprogramming.
2020 Bensalem, J., Hattersley, K. J., Hein, L. K., Tong Teong, X., Carosi, J. M., Hassiotis, S., . . . Sargeant, T. J. (2020). Measurement of autophagic flux in humans: an optimized method for blood samples.. Autophagy, 17(10), 3238-3255.
Scopus19 WoS18 Europe PMC152020 Whyte, L. S., Hassiotis, S., Hattersley, K. J., Hemsley, K. M., Hopwood, J. J., Lau, A. A., & Sargeant, T. J. (2020). Lysosomal Dysregulation in the Murine App<sup>NL-G-F/NL-G-F</sup> Model of Alzheimer's Disease. Neuroscience, 429, 143-155.
Scopus11 WoS10 Europe PMC72019 Mputhia, Z., Hone, E., Tripathi, T., Sargeant, T., Martins, R., & Bharadwaj, P. (2019). Autophagy modulation as a treatment of amyloid diseases. Molecules, 24(18), 3372-1-3372-20.
Scopus47 WoS43 Europe PMC302019 Cui, Y., Carosi, J. M., Yang, Z., Ariotti, N., Kerr, M. C., Parton, R. G., . . . Teasdale, R. D. (2019). Retromer has a selective function in cargo sorting via endosome transport carriers. Journal of Cell Biology, 218(2), 615-631.
Scopus97 WoS83 Europe PMC722019 Carosi, J. M., & Sargeant, T. J. (2019). Rapamycin and Alzheimer disease: a double-edged sword?. Autophagy, 15(8), 1460-1462.
Scopus62 WoS55 Europe PMC372019 Carosi, J. M., Hattersley, K. J., Cui, Y., Yang, Z., Teasdale, R. D., & Sargeant, T. J. (2019). Subcellular Fractionation of Hela Cells for Lysosome Enrichment Using a Continuous Percoll-Density Gradient. Bio-protocol, 9(18), 9 pages.
Scopus8 WoS5 Europe PMC42018 Hassiotis, S., Manavis, J., Blumbergs, P. C., Hattersley, K. J., Carosi, J. M., Kamei, M., & Sargeant, T. J. (2018). Lysosomal LAMP1 immunoreactivity exists in both diffuse and neuritic amyloid plaques in the human hippocampus. European Journal of Neuroscience, 47(9), 1043-1053.
Scopus31 WoS25 Europe PMC182018 Lloyd-Lewis, B., Krueger, C. C., Sargeant, T. J., D'Angelo, M. E., Deery, M. J., Feret, R., . . . Watson, C. J. (2018). Stat3-mediated alterations in lysosomal membrane protein composition. Journal of Biological Chemistry, 293(12), 4244-4261.
Scopus22 WoS20 Europe PMC182018 Gao, S., Casey, A. E., Sargeant, T. J., & Makinen, V. P. (2018). Genetic variation within endolysosomal system is associated with late-onset Alzheimer's disease. Brain, 141(9), 2711-2720.
Scopus55 WoS46 Europe PMC402017 Whyte, L. S., Lau, A. A., Hemsley, K. M., Hopwood, J. J., & Sargeant, T. J. (2017). Endo-lysosomal and autophagic dysfunction: a driving factor in Alzheimer's disease?. Journal of Neurochemistry, 140(5), 703-717.
Scopus97 WoS95 Europe PMC722017 Hein, L., Apaja, P., Hattersley, K., Grose, R., Xie, J., Proud, C., & Sargeant, T. (2017). A novel fluorescent probe reveals starvation controls the commitment of amyloid precursor protein to the lysosome. Biochimica et Biophysica Acta - Molecular Cell Research, 1864(10), 1554-1565.
Scopus16 WoS14 Europe PMC82017 Whyte, L. S., Hemsley, K. M., Lau, A. A., Hassiotis, S., Saito, T., Hopwood, J. J., & Sargeant, T. J. (2017). Reduction in open field activity in the absence of memory deficits in the AppNL-G-F knock-in mouse model of Alzheimer’s disease. Behavioural Brain Research, 336, 177-181.
Scopus47 WoS44 Europe PMC312017 Lloyd-Lewis, B., Sargeant, T. J., Kreuzaler, P. A., Resemann, H. K., Pensa, S., & Watson, C. J. (2017). Analysis of the involuting mouse mammary gland: An in vivo model for cell death. Methods in molecular biology (Clifton, N.J.), 1501, 165-186.
Scopus4 Europe PMC22016 Sargeant, T. J. (2016). Commentary: Possible involvement of lysosomal dysfunction in pathological changes of the brain in aged progranulin-deficient mice. Frontiers in Aging Neuroscience, 8(FEB), 3 pages.
Scopus4 WoS3 Europe PMC12015 Wooding, F. B. P., & Sargeant, T. J. (2015). Immunocytochemical Evidence for Golgi Vesicle Involvement in Milk Fat Globule Secretion. Journal of Histochemistry and Cytochemistry, 63(12), 943-951.
Scopus10 WoS8 Europe PMC62014 Sargeant, T. J., Lloyd-Lewis, B., Resemann, H. K., Ramos-Montoya, A., Skepper, J., & Watson, C. J. (2014). Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization. Nature Cell Biology, 16(11), 1057-1068.
Scopus117 WoS110 Europe PMC852014 Pensa, S., Lloyd-Lewis, B., Sargeant, T. J., Resemann, H. K., Kahn, C. R., & Watson, C. J. (2014). Signal transducer and activator of transcription 3 and the phosphatidylinositol 3-kinase regulatory subunits p55α and p50α regulate autophagy in vivo. FEBS Journal, 281(20), 4557-4567.
Scopus22 WoS19 Europe PMC202014 Campbell, J. J., Botos, L. A., Sargeant, T. J., Davidenko, N., Cameron, R. E., & Watson, C. J. (2014). A 3-D in vitro co-culture model of mammary gland involution. Integrative Biology (United Kingdom), 6(6), 618-626.
Scopus23 WoS23 Europe PMC172013 Al-Lamki, R. S., Lu, W., Wang, J., Yang, J., Sargeant, T. J., Wells, R., . . . Bradley, J. R. (2013). TNF, acting through inducibly expressed TNFR2, drives activation and cell cycle entry of c-Kit<sup>+</sup> cardiac stem cells in ischemic heart disease. Stem Cells, 31(9), 1881-1892.
Scopus20 WoS19 Europe PMC152012 Sargeant, T. J., Drage, D. J., Wang, S., Apostolakis, A. A., Cox, T. M., & Cachón-González, M. B. (2012). Characterization of Inducible Models of Tay-Sachs and Related Disease. PLoS Genetics, 8(9), 15 pages.
Scopus17 WoS14 Europe PMC102011 Sargeant, T. J., Wang, S., Bradley, J., Smith, N. J. C., Raha, A. A., McNair, R., . . . Cachón-González, M. B. (2011). Adeno-associated virus-mediated expression of β-hexosaminidase prevents neuronal loss in the sandhoff mouse brain. Human Molecular Genetics, 20(22), 4371-4380.
Scopus38 WoS36 Europe PMC312008 Sargeant, T. J., Miller, J. H., & Day, D. J. (2008). Opioidergic regulation of astroglial/neuronal proliferation: Where are we now?. Journal of Neurochemistry, 107(4), 883-897.
Scopus61 WoS55 Europe PMC382008 Sargeant, T. J., Day, D. J., Miller, J. H., & Steel, R. W. J. (2008). Acute in utero morphine exposure slows G<inf>2</inf>/M phase transition in radial glial and basal progenitor cells in the dorsal telencephalon of the E15.5 embryonic mouse. European Journal of Neuroscience, 28(6), 1060-1067.
Scopus26 WoS23 Europe PMC212007 Sargeant, T. J., Day, D. J., Mrkusich, E. M., Foo, D. F., & Miller, J. H. (2007). Mu opioid receptors are expressed on radial glia but not migrating neuroblasts in the late embryonic mouse brain. Brain Research, 1175(1), 28-38.
Scopus23 WoS23 Europe PMC16
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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 2022 Co-Supervisor The Evaluation and Validation of Autophagy as a Novel Biomarker of Coronary Artery Disease Doctor of Philosophy Doctorate Part Time Dr Mau Tam Nguyen -
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 2018 - 2022 Co-Supervisor The Role of Rheb in Regulating mTORC1 and Cellular Function Doctor of Philosophy Doctorate Full Time Mr Stuart Paul De Poi 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
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