Using mini-brains to see how brain cells are affected by altered NF-kB

Dr Jun Yan

University of Queensland, QLD

| Causes and Prevention | Immunology | Incubator | 2021 | Investigator Led Research |
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Summary

Dr Jun Yan and her team are interested in a molecular pathway called the NF-kB pathway that is present in cells throughout the body and controls many basic functions of cells. However, the NF-kB pathway doesn't operate in the same way in all types of cells. In immune cells, activating the NF-kB pathway causes inflammation. In contrast, in brain cells, activating the NF-kB pathway appears to be beneficial, allowing the formation of new memories as well as protecting nerve cells from damage.

Dr Yan’s team have previously found that people with MS have a lower-than-normal level of a molecule, called IkB-a, that blocks the NF-kB pathway. This means that immune cells in people with MS tend to be more activated and inflammatory than those in other people.

Currently, there is nothing known about how the lower-than-normal levels of IkB-a seen in people with MS might affect the cells in the brain. A complicating factor in studying this is that we cannot study pieces of people's brains to look at the effects of low levels of IkB-a. Therefore, we will explore whether we can use a type of stem cell called an induced pluripotent stem cell (iPSC) to produce brain cells and brain organoids (mini brains in a dish) that can be used to look at the effects of low levels of IkB-a in brain cells.

Project Outcomes

In this study, Dr Jun Yan and her team achieved three key outcomes. Firstly, they successfully derived important brain cells; neurons and astrocytes from human-induced pluripotent stem cells (iPSCs) and prepared brain organoids for a period of up to 12 weeks in a laboratory setting. Secondly, they were able to effectively reduce the levels of IkB-a in iPSC-derived brain cells. Lastly, they conducted investigations into the level of NF-kB in brain organoids at different stages of development.  

These outcomes demonstrate significant progress in the development of a model system using iPSC-derived brain cells and organoids to explore the effects of IkB-a levels on brain cells and NF-kB expression. The team are now finalising their findings for publication.

Updated: 31 March 2023

Updated: 16 November, 2021

Stages of the research process

Fundamental laboratory
Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline: 10+ years
Translational
Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline: 5+ years
Clinical Studies
and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline: 1-5 years

Investigator

Co-investigator

Grant Awarded

  • Incubator Grant

Total Funding

  • $25,000

Duration

  • 2 years

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Using mini-brains to see how brain cells are affected by altered NF-kB