Understanding brain development & disease

Confocal microscope image of zebrafish embryos

Zebrafish embryos four days post fertilisation (four days “old”) highlighting brain areas with mir-9 activity such as the telencephalon and hypothalamus in green, and neuronal processes in red, as well as the large larval eye. Images by Fansuo Geng

Developmental Neurobiology & Genomics

As the brain and nervous system develop there must be a balance between increasing the cell count (proliferation), and ensuring the cells reach maturity (differentiation).

The timing at which immature progenitor cells undergo their final division must be tightly controlled and coordinated to ensure the each cell type is present in the right number.

Professor Becker and his team in the Developmental Neurobiology & Genomics Program studied a genetic regulatory element called micro RNA 9 (miR-9) and found that rather than acting as a developmental switch between cell proliferation and cell differentiation, miR-9 facilitates the transition of immature progenitor cells towards their final division to become fully mature cells.

miR-9 was found to be active at late stages of embryonic development, when nerve cell production reaches its peak.

This finding helps to further describe the genetic processes involved in brain development in the model organism, providing an important platform for further studies of human brain development and how it is implicated in disease.

Providing a deeper understanding of cofilin and Alzheimer’s disease

Alzheimer's Cell Biology

Researchers in the Alzheimer’s Cell Biology Program are investigating the effects of Alzheimer’s disease on the cytoskeleton – the dynamic protein scaffold or skeleton by which the body’s cells maintain their structure and shape and carry out a diverse range of essential functions.

Led by Dr Claire Goldsbury, the team are comparing the distribution of cofilin between the post-mortem brains of people who experienced normal ageing with those affected by Alzheimer’s or Huntington’s diseases. This comparison will reveal whether cofilin is a critical element of these diseases.

The results may change our understanding of the disease process.

Nerve-attacking antibodies in inflammatory diseases of the peripheral nervous system

confocal microscope image of the Node of Ranvier

Antibodies in serum (green) from patients with inflammatory neuropathy bind to the Node of Ranvier and interfere with the critical functioning of neural transmission.

Inflammatory Neuropathies

Guillain Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) occur when the immune system mistakenly attacks the peripheral nerves. One of the most important unanswered questions in peripheral nerve research is what exactly the immune system is attacking.

In 2012, researchers in the Neuroinflammation Group applied serum from patients with GBS and CIDP to teased nerve fibres to determine the nerve targets of the immune system. They discovered that antibodies in the blood not only strip myelin off the nerve fibres, but in some cases find gaps in the nerve covering, called the Node of Ranvier and surrounding areas, all of which are critical to the functioning of the nerve.

Ongoing work is focussed on identifying the proteins targeted by the antibodies at these sites in order to better determine exactly what the immune system is attacking.