Dr Tim Sadlon

• Biography/ Background

  Dr Sadlon is a Senior Research Fellow in the Molecular Immunology Laboratory led by Professor Simon Barry at the University of Adelaide and Women’s and Children’s Hospital. My research interests encompass both basic and translational science and are focused on understanding how the immune system is regulated in normal and pathological conditions such as autoimmunity and cancer.

• Qualifications

  Bachelor of Science Degree, 1987. University of Adelaide Adelaide, South Australia

  
  Honours in Biochemistry, 1988. University of Adelaide Adelaide, South Australia

  Awarded Ph. D. 1996. Department of Biochemistry, University of Adelaide.
  Thesis title: "Regulation of the Rat 5-Aminolevulinate Synthase mRNA: the Role of mRNA Stability."
  Supervisor: A/Prof B. K. May

   

   

• Teaching Interests

  Date	Role	Research Topic	Program	Degree Type	Student Load	Student Name
  2022	Co-Supervisor	Optimisation of Chimeric Antigen Receptor T Cells for Pan Solid Tumour Immunotherapy	Doctor of Philosophy	Doctorate	Full Time	Mr Jieren Zheng
  2022	Co-Supervisor	Functional validation of enhancers linked with Type 1 Diabetes using CRISPR Cas9 tools.	Doctor of Philosophy	Doctorate	Full Time	Miss Leela Amy Balin
  2021	Co-Supervisor	The Development of Chimeric Antigen Receptor Regulatory T cells (CAR-Tregs) as a Novel Therapy for Autoimmune-driven Type 1 Diabetes (T1D)	Doctor of Philosophy	Doctorate	Full Time	Ms Jacqueline Claire Scaffidi
  2019	Co-Supervisor	Does the SATBI superenhancer prevent autoimmunity in mice?	Doctor of Philosophy	Doctorate	Full Time	Miss Katherine Alexandra Brown
  2017 - 2021	Co-supervisor	The Identification Of Genetic And Epigenetic Changes That Contribute To Type 1 Diabetes	Doctor of Philosophy	Doctorate	Full Time	Dr Ying Ying Wong
  2016 - 2021	Co-Supervisor	A NOVEL ROLE FOR ZEB2 AS A LINEAGE FIDELITY CHECKPOINT IN HUMAN CD4+ T CELLS	Doctor of Philosophy	Doctorate	Full Time	Mr Soon Wei Wong
  2009 - 2013	Co-Supervisor	A Tumour Suppressor Role for FOXP3 and FOXP3-regulated MicroRNAs in Breast Cancer Cells	Doctor of Philosophy	Doctorate	Full Time	Miss Natasha McInnes

• Research Interests

  Dr Sadlon is a Senior Research Fellow in the Molecular Immunology Laboratory led by Professor Simon Barry at the University of Adelaide and Women's and Children's Hospital. My research interests encompass both basic and translational science and are focused on understanding how the immune system is regulated in normal and pathological conditions such as autoimmunity and cancer.

  I apply cell and molecular biology approaches to the study of human regulatory T (Treg) cells, that keep the immune system in balance and promote immune tolerance. Defects in Treg cells contribute to autoimmune diseases but the molecular nature of these defects remain largely unknown. Genome wide association studies (GWAS) indicate that a significant proportion of the genetic risk associated with autoimmune disease co-localises with T cell specific enhancers, transcriptional regulatory elements which control gene expression in these cells. Identifying the target genes controlled by these enhancers may hold the key to understanding autoimmune diseases. To this end, I am employing genome-wide approaches including Chromatin immunoprecipitation, chromosome conformation capture, ATAC-seq (Assay of Transposase Accessible Chromatin with high throughput sequencing) and RNAseq to discover three-dimensional enhancer - target gene interactions that underpin the Treg transcriptome in health and disease. My research has several areas of focus:

  Identification of genetic and epigenetic changes that contribute to Type 1 Diabetes.
  Type 1 Diabetes (T1D) is one of the most serious and common chronic diseases of childhood in Australia. Triggers for T1D are unknown, no cures currently exist and, for a significant proportion of individuals, results in serious complications in later life. We are using multiple genomics approaches comparing matched T1D and healthy control samples to detect disease-associated changes at gene enhancers, linking these enhancers to their target genes and correlating this with gene expression changes.

  Investigating the role of the chromatin organizer special AT rich binding protein 1 (SATB1) in autoimmune disease.
  This work builds on our discovery that SATB1 is a key target of the Treg master transcriptional factor FOXP3. Using chromosome conformation capture we have linked SATB1 to an enhancer cluster located hundreds of kilobases away from the gene. Importantly, this enhancer cluster overlaps genetic risk loci associated with multiple autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, and inflammatory skin disease. Our mouse enhancer knockout models have confirmed this enhancer region regulates SATB1 and that the resultant change in SATB 1 levels alters the pathogenic potential of CD4+ T cells, a subset of T cells that include Tregs. Current efforts are focused on a detailed characterisation of the interplay between disease-associated variation, enhancer function and SATB1 regulation in T cells to uncover how alterations at this single regulatory region can be linked to multiple different diseases.

  Translational research.
  My interest in Translational research includes the development of cellular immunotherapies to treat solid tumours and T1D. I work with a Biotech start-up, Carina Biotech, to develop chimeric antigen receptor (CAR) T cells as an anticancer therapy for solid tumours. A second project seeks to migrate the knowledge we have gained in the CAR T cell space to develop CAR Treg technology, for the treatment of T1D. Here we aim to show that Tregs engineered to express a CAR that recognises pancreatic islet antigens can protect the pancreatic beta-cells from auto-immune destruction.

   

• Research Funding

  (2021-2023) Co-Investigator. JDRF Pilot and Innovation Grant ($505K). Connecting genetic risk to genes: Turning targets into new interventions

  (2020) Chief Investigator A. Women’s and Children’s Hospital Foundation Grant ($100K) Identifying effector T cell responses to T regulatory cell suppression at the single cell level: discovering new approaches that induce tolerance to treat autoimmunity and cancer.

  (2018) Chief Investigator A Channel 7; CRF. ($75K). Chimeric Antigen Receptor Tregulatory cells (CAR-Treg) as a treatment for Type 1 Diabetes (TID)

  (2017) Chief Investigator A. Women’s and Children’s Hospital Foundation Grant ($75K). The identification of genetic and epigenetic changes that contribute to T1D by ATAC-seq (Assay of Transposase Accessible Chromatin with high throughput sequencing).

  (2017) Chief Investigator A. RRI Innovation Seed Funding Program. ($25K). In vivo functional validation of a disease linked super enhancer in IBD.

  (2015) Chief Investigator A. RRI Innovation Seed Funding Program. ($25K). The role of distal regulatory elements in setting SATB1 expression levels in Tregs; implications in autoimmune disease and maternal immune tolerance to the foetus.

  (2015) Chief Investigator A. Women’s and Children’s Hospital Foundation Grant ($75K). High-resolution capture Hi-C to map long-range promoter contacts that control human regulatory T cell function to reveal key molecular defects in autoimmune disease.

  (2012) Chief Investigator A; Women’s and Children’s Hospital Foundation Grant ($50,000). A FOXP3 and PRDM1-dependent pathway is required for IL10 induction in human T regulatory cells; role of this pathway in the generation and function of inducible Treg cells.

   

   

• Publications

• Professional Associations

  Australian and New Zealand Society for Immunology member (2011- ) 

Entry last updated: Friday, 7 Jul 2023