Immune Development

Unlocking secrets of immunity and autoimmunity 

Our laboratory is unravelling the mysteries of our immune system using human pluripotent stem cells. Led by Professor Ed Stanley, we create immune cells to help us understand how our body defends itself against infections and why it sometimes falters, causing autoimmune diseases like type 1 diabetes. 

In addition to immune cells, we also make the tissue cells that our immune system interacts with, such as insulin-producing pancreatic cells. Like detectives recreating a crime scene, we mix our immune cells and tissue cells to understand how they talk to each other in the body.  

To study autoimmunity, we make immune cells resembling those of people who have type 1 diabetes. These cells are then combined with pancreatic insulin-producing cells to recreate the autoimmune environment. We can then observe the interaction between these actors, helping us to understand why immune cells turn against their own body.   

In the Immune Development Laboratory, we blend science and innovation to create a healthier world for children fighting infections and living with autoimmune diseases. By uncovering the inner workings of our immune system, we are contributing to the development of new treatments, cellular therapies and perhaps one day, potential cures.

What we see under the microscope

This artwork below by Kathleen Strumila is Inspired by transmission electron microscopic imagery. It illustrates macrophages (red) as the immune system's vigilant "police," detecting and eliminating harmful invaders like mycobacteria (green),

More information

• Our team collaborates with the reNEW international consortium on numerous key projects from reNEW Melbourne and with our colleagues in Denmark and the Netherlands. 
• New international stem cell research centre offers hope for patients with incurable diseases 
• Global stem cell research partnership launches to advance treatment for incurable diseases  
• Immune cell model paves the way for new treatments targeting common infection amongst immunocompromised children 
• Human immune cells produced in a dish in world's first 

Our projects

Modelling immunity and autoimmunity.

We are making immune cells from induced pluripotent stem cells derived from healthy individuals and people with type 1 diabetes. To study infections we are using these immune cells to build complex models or ‘organoids’ that mimic the human lung.

To study autoimmunity we are researching the insulin-producing cells of the pancreas. Using our lung organoids, we can add microbes that cause infections to model what happens in real life. Similarly, we can mix immune cells with pancreatic cells to understand why the immune system attacks the cells that make insulin. This helps us learn about how our immune system works and why sometimes it doesn't work properly. We hope this will help us find new ways to treat infections and autoimmune disorders.

Making insulin-producing cells

We are developing new and more efficient methods in the laboratory to make insulin-producing beta cells from pluripotent stem cells. We are focused on making beta cells in the laboratory that can exactly match an individual with the hope of using these cells to help people with type 1 diabetes in the future.

Currently, we're concentrating on using our laboratory-made cells to learn about how they interact with the immune system in a way that mimics the mechanisms of our bodies. This will help us understand more about diabetes and how to treat it better.

Building better models to study respiratory diseases

We have a group of researchers dedicated to learning more about diseases that affect our respiratory system. For this project, we are using induced pluripotent stem cells to create key cell types in our lungs and combining these in a dish to construct “mini lungs”. We then use these models to understand how viruses and bacteria infect our lungs, and why some people are more likely to suffer severe or frequent infections.

We’re interested in studying both common causes of lung infections, such as respiratory syncytial virus, rhinovirus and influenza, as well as rare and/or deadly infections, like SARS-CoV-2 and Mycobacterium abscessus. We're also interested in understanding chronic lung problems, like asthma, pulmonary fibrosis and rare causes of interstitial lung disease. Our ultimate goal is to find new drugs to treat these diseases and infections.

Funding

• Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW (Grant Number NNF21CC0073729)
• National Health and Medical Research Council (NHMRC)
• CSL Limited
  
  

Collaborations

Collaborations with scientists at Murdoch Children’s Research Institute:

• Professor Andrew Elefanty
• Associate Professor Elizabeth Ng
• Associate Professor Shireen Lamande
• Associate Professor Dan Pellicci
• Dr Sohinee Sarkar
• Professor Sarath Ranganathan
• Dr Shivanthan Shanthikumar
• Dr Melanie Neeland
• Associate Professor Richard Mills
• Professor Andrew Steer
• Associate Professo Paul Licciardi
• Associate Professor Catherine Satzke

Other collaborators

• Stuart Mannering, St Vincent’s Institute of Medical Research, Melbourne, Australia
• Tom Kay, St Vincent’s Institute of Medical Research, Melbourne, Australia
• Helen Thomas, St Vincent’s Institute of Medical Research, Melbourne, Australia
• Tom Loudovaris, St Vincent’s Institute of Medical Research, Melbourne, Australia
• Josh Brickman, University of Copenhagen, Copenhagen, Denmark
• Eelco de Koning, Leiden University Medical Centre, Leiden, Netherlands
• Jakub Sedzinski, University of Copenhagen, Copenhagen, Denmark

Featured publications

Human pluripotent stem cell-derived macrophages host Mycobacterium abscessus infection. Sun S, Stanley EG et al. Stem Cell Reports. 2022 Sep 13;17(9):2156-2166. Epub 2022 Aug 18. PMID: 35985333.

Multipotent RAG1+ progenitors emerge directly from haemogenic endothelium in human pluripotent stem cell-derived haematopoietic organoids. Motazedian A, Stanley EG et al., Nature Cell Biology. 2020 Jan;22(1):60-73. Epub 2020 Jan 6.

Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes. Joshi K, Stanley EG et al., Diabetologia. 2019 Dec;62(12):2245-2251.

Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros. Ng ES…Stanley EG et al., Nat Biotechnol. 2016 Nov;34(11):1168-1179.

GAPTrap: A Simple Expression System for Pluripotent Stem Cells and Their Derivatives. Kao T…Stanley EG et al., Stem Cell Reports. 2016 Sep 13;7(3):518-526.

CRISPR interference interrogation of COPD GWAS genes reveals the functional significance of desmoplakin in iPSC-derived alveolar epithelial cells. Werder, R.B et al., Science Advances, 2022. PMID: 35857525.

Adenine Base Editing Reduces Misfolded Protein Accumulation and Toxicity in Alpha-1 Antitrypsin Deficient Patient iPSC-Hepatocytes. Werder, R.B. et al.  Molecular Therapy, 2021. PMID: 34217893.