How nerve impulses are generated in the brain
Neuronal Signalling Group
Research Fellow Dr Maarten Kole, along with Professor Greg Stuart and other members of the Neuronal Integration Laboratory,
Neuroscience Program, have been working to increase our understanding of the way in which the nerve impulse, or action
potential, is generated in nerve cells of the brain. Action potentials are the primary electrical signals used for fast communication
between nerve cells. From previous research, it is known that action potentials are generated in a region of the nerve cell axon
(the main output pathway of neurons) called the axon initial segment. In two separate papers published in the prestigious
journal Nature Neuroscience, Kole, Stuart and colleagues have described the cellular and molecular mechanisms leading to
action potential generation, showing that it is the result of a high density of voltage-activated sodium channels in the axon
initial segment, which are tightly bound to the actin cytoskeleton. These sodium channels open as a result of a changed voltage
across the cell membrane, allowing positively charged sodium ions to flow inwards, resulting in the generation of a single site
with low action potential threshold and subsequently the triggering of the action potential. Collectively, these studies describe
for the first time the fundamental cellular mechanisms used by neurons to generate electrical impulses, enabling complex neural
processing of the brain.

Kole, M.H.P., Ilschner, S.U., Kampa, BM, Williams, S.R., Ruben, PC and Stuart, G.J. (2008) Action potential generation requires a
high sodium channel density in the axon initial segment. Nature Neuroscience 11(2): 178-186

Kole, M.H.P. and Stuart, G.J. (2008) Is action potential threshold lowest in the axon? Nature Neuroscience 11(11):1253-1255

Overturning the one cell — one antibody dogma
Cancer and Vascular Biology Group
Postdoctoral fellow Ben Quah, along with Professor Chris Parish and collaborators in the Divisions of Immunology and Molecular
Bioscience JCSMR published the groundbreaking discovery that B lymphocytes - the immune cells responsible for making
antibodies - share these antibodies with one another. Current concepts of immunity are based firmly upon Nobel-prize winning
Australian immunologist Mac Burnet’s concept of ‘clonal selection’. In that view, each immune cell is restricted to making a
single, unique antibody, so that production of a particular antibody can only be built up after a single cell has replicated into
clonal copies many times. While the genes encoding antibodies are indeed subject to Burnet’s laws of one cell- one antibody,
Quah, Parish and their colleagues discovered that the antibody proteins themselves are efficiently passed among different cells
so that one cell can borrow a useful antibody made by another. This remarkable violation of the clonal selection dogma may help
the immune system respond more rapidly to an infection, and points to a new process in cell biology that may have ramifications
well beyond the immune system.

Quah, B.J.C., Barlow, V.P., McPhun, V., Matthaei, K.I., Hulett, M.D. and Parish, C.R. (2008) Bystander B cells rapidly acquire antigen
receptors from activatedB cells by membrane transfer. Proceedings of the National Academy of Sciences of the United States of
America 105(11):4259-4264

Discovering mechanisms of memory in the immune system: parallels with
mechanisms of memory in the brain
Immunogenomics Group
PhD student Zuopeng Wu published the discovery of a new gene and mechanism essential for the immune system to produce
the class of T cells that ‘remember’ an infection or immunization and resist re-infection His paper – co-authored with JCSMR
supervisors Gerard Hoyne and Chris Goodnow and collaborators in Gottfried Otting’s group in the ANU Research School of
Chemistry and at the Institute for Systems Biology in Seattle — featured on the cover of the prestigious journal Immunity. It
revealed that a previously obscure protein, hnRNPLL, dramatically changes the splicing of messenger RNA molecules in memory
T cells — changing the characteristics and longevity of the T cells much as a film editor can alter the plot of a film by splicing
different scenes in and out. Remarkably, both the general strategy of altered splicing and the specific ‘scenes’ affected in
memory T cells overlaps with emerging findings about RNA splicing changes occurring during the formation of memory in the
brain. Thus, the study not only reveals a specific mechanism for memory in the immune system, but also a general strategy used
in immune cells and brain cells.

Wu, Z., Jia, X., de la Cruz, L., Su, X., Marzolf, B., Troisch, P., Zak, D., Hamilton, A., Whittle, B., Yu, D., Sheahan, D., Bertram, E.,
Aderem, A., Otting, G., Goodnow, C.C. and Hoyne, G.F. (2008) Memory T cell RNA rearrangement programmed by heterogeneous
nuclear ribonucleoprotein hnRNPLL. Immunity 29(6):863-875

The role of calsequestrin in skeletal muscle contraction
Muscle Research Group
Dr Nikki Beard, Postdoctoral Fellow in the Muscle Research Group headed by Professor Angela Dulhunty, has worked with
colleagues including other members of the Group and Magdolna Varsányi from Ruhr-Universität, Bochum, Germany to
understand the mechanisms by which the skeletal muscle calcium binding protein calsequestrin plays a role in controlling
muscle contraction. Published in the journal Cell Calcium, this research shows for the first time that phosphorylation of
calsequestrin enhances its capacity to bind calcium. Appropriate binding of calcium is essential to the proper functioning of
skeletal muscle in the regulation of movement. Additionally, this research identified an accessory protein, junctin, as being
essential in mediating regulation of muscle contraction by calsequestrin.
Beard, N.A., Wei, L., Cheung, S.N., Kimura, T., Varsanyi, M. and Dulhunty, A.F. (2008) Phosphorylation of skeletal muscle
calsequestrin enhances its Ca2+ binding capacity and promotes its association with junctin. Cell Calcium 44(4):363-373
muscle contraction. Published in the journal Cell Calcium, this research shows for the first time that phosphorylation of
calsequestrin enhances its capacity to bind calcium. Appropriate binding of calcium is essential to the proper functioning of
skeletal muscle in the regulation of movement. Additionally, this research identified an accessory protein, junctin, as being
essential in mediating regulation of muscle contraction by calsequestrin.

Beard, N.A., Wei, L., Cheung, S.N., Kimura, T., Varsanyi, M. and Dulhunty, A.F. (2008) Phosphorylation of skeletal muscle
calsequestrin enhances its Ca2+ binding capacity and promotes its association with junctin. Cell Calcium 44(4):363-373

Science Minister’s Prize for Life Scientist of the Year
• Dr Carola Garcia de Vinuesa was awarded the Science Minister’s Prizefor Life Scientist of the Year at the Prime Minister’s Prizes for Science.
The award celebrates the achievements of an outstanding early career researcher. Dr Vinuesa currently leads a team of ten people at JCSMR, and received the award in recognition for her work on the quality control of antibodies, which has helped uncover causes of autoimmune diseases like Type 1 diabetes and lupus.

Member of the Order of Australia
• Professor Steve Redman AM, was honoured with a Member of the Order of Australia, General Division in the Queen’s Birthday
Honours list. Professor Redman’s award was for services to medical science, particularly in the field of experimental neuroscience
as an academic and researcher and through contributions to professional organisations.

Adrien Albert Award
• Professor Jill Gready received The Adrien Albert Award from The Division of Biomolecular Chemistry of The Royal Australian Chemical Institute Inc. at their conference in July. This prestigious award is named for Professor Adrien Albert, Chair of The Department of Medical Chemistry at JCSMR from its inception in 1948 until his retirement in 1972.

Australian Society for Biophysics
• Professor Angela Dulhunty, Division of Molecular Bioscience, was elected President of the Australian Society for Biophysics.