Congratulations to our 2022 NHMRC Ideas grant awardees

L-R: Dr Omer Gilan, A/Prof Margaret Hibbs, Prof Vaughan Macefield

and Prof Merlin Thomas

Congratulations to Central Clinical School's (CCS) four National Health and Medical Research Council (NHMRC) awardees Professor Vaughan Macefield, Associate Professor Margaret Hibbs, Professor Merlin Thomas and Dr Omer Gilan in this very difficult round. 

See detail below of CCS research and see all Monash Faculty winners here.

Prize for PhD student Lakshanie Wickramasinghe's research on neonatal lung diseases

Ms Lakshanie Wickramasinghe, PhD student in the Department of 
Immunology and Pathology, wins Royal Society of Victoria prize

Congratulations to Ms Lakshanie Wickramasinghe, who has been awarded the 2020 Royal Society of Victoria Young Scientist Research Prize in Biomedicine and Health Sciences. Well done Lakshanie!

Lakshanie is doing her PhD in Central Clinical School's Department of Immunology and Pathology, supervised by Associate Professor Margaret Hibbs. Her PhD is on “Granulocyte Colony-Stimulating Factor: A new target in neonatal lung disease”.

2019 CCS research highlights: Department of Immunology and Pathology

L-R: Profs Ben Marsland, Margaret Hibbs

Monash University's Central Clinical School is at the cutting edge of medical research in national and international arenas. We are publishing a series of our research highlights from across 2019.

In this article we feature two highlights from the Department of Immunology and Pathology.

• World-first study of newborn airways microbiome may help prevent childhood asthma  
• Study raises hope for new lung disease treatment

Grant win for Dr Bridgette Semple

Congratulations to Dr Bridgette Semple, who has been awarded the 2019 Capstone Editing Grant for Mid-Career Researchers!

Dr Bridgette Semple (left)

Capstone Editing, an Australian academic editing company, supports one researcher annually to undertake an innovative research project with a view to gathering preliminary data that will lead to the development of a research council funding application.

Dr Semple is the Head of the Paediatric Neurotrauma Group in the Department of Neuroscience.  Her research focuses on traumatic brain injury, particularly during early childhood. The funds from this grant will assist with her collaboration with Associate Professor Margaret Hibbs from the Immunology Department.  They will investigate the role of the SHIP-1 enzyme, which is yet to be explored in the brain.

Congratulations to our recently completed PhD students!

Congratulations Timothy (pictured)
and Annas!

Congratulations to our recently completed PhD students, Mr Timothy Gottschalk and Mr Annas Al-Sharea! We wish them well for their future scientific careers.

Monash findings offer hope for new lung disease drug

Associate Professor Margaret Hibbs' group. There are a number
of co-authors on the paper which has identified a protein important
for controlling emphysema. L-R: Dr Evelyn Tsantikos, Ms Cassandra
Castelino, Ms April Raftery, Associate Professor Margaret Hibbs,
Mr Tim Gottschalk, Ms Lakshanie Wickramasinghe, Dr Maverick
Lau, Dr Jess Borger

by Anne Crawford

Monash University researchers have identified a critical role for a protein known as G-CSF in chronic obstructive pulmonary disease (COPD), an incurable lung disease often referred to as emphysema.

COPD is the third most common cause of death worldwide, afflicting 29% of people over 75 in Australia and its incidence is increasing. It responds poorly to current therapies, which have remained largely unchanged for decades.

The multi-disciplinary research team, led by Associate Professor Margaret Hibbs from the Department of Immunology and Pathology, showed that lung disease and other disease comorbidities such as osteoporosis, heart disease and body wasting failed to develop in an experimental COPD model when G-CSF was “knocked out” genetically. They also demonstrated that G-CSF levels were elevated in the lungs of patients with COPD, suggesting it played a destructive role.

Preventing the development of multi-organ autoimmunity

By Dr Jodie Abramovitch

Autoimmune disease occurs when the immune system incorrectly recognises self-tissues and organs as being potentially dangerous - like a pathogen. The immune system attacks the tissue or organ – sometimes in an organ-specific manner (eg. type I diabetes) or sometimes in a multi-organ fashion (eg. lupus) – which leads to disease symptoms. What causes the onset of autoimmune disease is not well understood and, consequently, there is no cure with treatments predominantly aimed at relieving inflammatory symptoms.

Elisha de Valle - first author of this study

In a collaborative study, Monash researchers examined the role of transcription factor NF-κB1 in a specific type of immune cell, Follicular B cells (Fo B cells), and its role in controlling multi-organ autoimmune disease. NF-κB1 is important for regulating B cell function and when Fo B cells become deregulated they can produce antibodies that target and destroy vital organs. The authors of this study used a mouse model that lacks the NF-κB1 gene and analysed the effect on Fo B cells. They found that Fo B cells lacking NF-κB1 secreted a large amount of pro-inflammatory factor IL-6 and this had an effect on surrounding immune cells. Specifically, IL-6 led to the over stimulation of B cells which resulted in the formation of  germinal centre structures (sites where antibody responses are launched) and, in turn, an increase in the presence of self-reacting antibodies against self-tissues and organs within the NF-κB1 deficient mice. Moreover, IL-6 also caused Fo B cells to proliferate at a higher rate which exacerbated the germinal centre B cell response. Without NF-κB1, the mice developed severe multi-organ autoimmune disease and had a reduced life span compared to healthy mice. This was largely attributable to the production of IL-6 by Fo B cells. Importantly, when IL-6 was blocked the development of autoimmune disease was greatly reduced.

This study revealed that NF-κB1 has an essential role in controlling the function of Fo B cells, primarily to limit the production of inflammatory factor IL-6. In the absence of NF-κB1, the production of IL-6 becomes deregulated and severe autoimmune disease can occur. These conclusions further the understanding of the mechanisms that control IL-6 production and may lead to better management of patients with autoimmune disease.

Reference: de Valle E, Grigoriadis G, O'Reilly LA, Willis SN, Maxwell MJ, Corcoran LM, Tsantikos E, Cornish JK, Fairfax KA, Vasanthakumar A, Febbraio MA, Hibbs ML, Pellegrini M, Banerjee A, Hodgkin PD, Kallies A, Mackay F, Strasser A, Gerondakis S, Gugasyan R. NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells. J Exp Med. 2016 Apr; 213:621-41. 

doi: 10.1084/jem.20151182.

Recent CCS publications: Week ending 22 April 2016

Transcranial stimulation

Recent publications with Central Clinical School affiliated authors:

Duan M, Steinfort DP, Smallwood D, Hew M, Chen W, Ernst M, Irving LB, Anderson GP, Hibbs ML. CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs. Mucosal Immunol. 2016 Mar;9(2):550-63. 
Link: doi 10.1038/mi.2015.84.

Fitzgerald, P.B., Hoy, K.E., Elliot, D., McQueen, S., Wambeek, L.E., Daskalakis, Z.J. A negative double-blind controlled trial of sequential bilateral rTMS in the treatment of bipolar depression. Journal of Affective Disorders (2016) 198 pp. 158 - 162
Link: doi: 10.1016/j.jad.2016.03.052
 
Lim HY, Ng C, Donnan G, Nandurkar H, Ho P. Ten years of cerebral venous thrombosis: male gender and myeloproliferative neoplasm is associated with thrombotic recurrence in unprovoked events. J Thromb Thrombolysis. 2016 Apr 16. [Epub ahead of print]
Link: PMID 27085541

Maller JJ, Anderson RJ, Thomson RH, Daskalakis ZJ, Rosenfeld JV, Fitzgerald PB. Occipital bending in schizophrenia. Aust N Z J Psychiatry. 2016 Apr 11. pii: 0004867416642023. [Epub ahead of print]
Link: PMID 27066817

Recent CCS publications: Week ending 15 April 2016

Figure 2 from the Darido publication: A schematic representation
of the cross-talk among key barrier genes, signaling transducers
and inflammatory factors

Recent publications with Central Clinical School affiliated authors:

Darido C, Georgy SR and Jane SM. The role of barrier genes in epidermal malignancy. Oncogene advance online publication 4 April 2016; 
Reference doi: 10.1038/onc.2016.84

de Valle E, Grigoriadis G, O'Reilly LA, Willis SN, Maxwell MJ, Corcoran LM, Tsantikos E, Cornish JK, Fairfax KA, Vasanthakumar A, Febbraio MA, Hibbs ML, Pellegrini M, Banerjee A, Hodgkin PD, Kallies A, Mackay F, Strasser A, Gerondakis S, Gugasyan R. NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells. J Exp Med. 2016 Apr; 213:621-41. 
Reference doi: 10.1084/jem.20151182.

Philpott AL, Fitzgerald PB, Bailey NW, Churchyard A, Georgiou-Karistianis N, Cummins TD. A GABBR2 gene variant modifies pathophysiology in Huntington's disease. Neurosci Lett. 2016 Mar; 620:8-13.
Reference doi: 10.1016/j.neulet.2016.03.038.

Prichard R, Rossi M, Muir J, Yao C, Whelan K, Lomer M. Fermentable oligosaccharide, disaccharide, monosaccharide and polyol content of foods commonly consumed by ethnic minority groups in the United Kingdom. Int J Food Sci Nutr. 2016 Mar:1-8 (online).  
Reference doi: 10.3109/09637486.2016.1163328

Removal of B1b B cells protective against lupus

2015 Mackay group. L-R: Beatriz Garcillan, Aurelie Baldolli, Fabien Vincent, Ellen McAllister, Fabienne Mackay, Angela Nguyen, Pin Shie Quah, Rachel Lim, Florence Lim, Will Figgett

By Dr Jodie Abramovitch

Systemic lupus erythematosus (SLE), commonly known as lupus, is an autoimmune disease with no cure. Monash researchers have been working to understand the immunological causes of lupus in a mouse model so as to better understand the disease in humans. Such groundwork will enable the development of much more effective therapies for the treatment of lupus.

Professor Fabienne Mackay (former head of the Department of Immunology and Pathology), together with the department's Leukocyte Signalling laboratory headed by Associate Professor Margaret Hibbs  have discovered that a certain type of innate B cell (immune cell), known as a B1b B cell, may be critical in the development of lupus.

Two types of mature B cells that are activated by toll-like receptor (TLR) signalling are B1 B cells and marginal zone (MZ) B cells. In the mouse model studied, these cells cause disease by infiltrating various tissues such as the salivary glands and kidneys. When the MZ and B1a B cells were removed from the mice, disease still occurred. When B1b B cells were removed also, mice were protected from all symptoms of lupus. Therefore B cells and CD19 signalling, specifically innate B cells, are very important in the development of lupus and may represent a target for treatment.

Reference: Fairfax KA, Tsantikos E, Figgett WA, Vincent FB, Quah P, LePage M, Hibbs ML, Mackay F. BAFF driven autoimmunity requires CD19 expression. J Autoimmun. 2015 Aug; 62: 1-10
doi:10.1016/j.jaut.2015.06.001

CCS successes in 2015 NHMRC funding

CCS awards 'Near Miss' funding to Kate Hoy, Catriona Bradshaw and Margaret Hibbs

Dr Kate Hoy

Dr Margaret Hibbs

Dr Catriona Bradshaw

The CCS has expanded its near miss funding program this year to provide additional support to investigators affected by the tightening of NHMRC purse strings. Three grants that all scored Category 5 quartile 4 and participated in the CCS review process will be awarded $100,000 each. Congratulations to our awardees this year, Dr Kate Hoy (MAPRc), Dr Catriona Bradshaw (Melbourne Sexual Health) and Dr Margaret Hibbs (Immunology).

Central Clinical School (CCS) funds 'Near Miss' grants

This year though there were many highly ranked grant applications for NHMRC funding, the overall percentage of applications funded was substantially down. CCS gave $150,000 for the two most highly ranked grant applications which missed out. Congratulations to the two 'Near Miss' grant recipients, A/Prof Margaret Hibbs and Prof Jenny Wilkinson-Berka.

Slowing down SLE kidney disease

Systemic lupus erythematosus (SLE), more simply known as lupus, is an autoimmune disease where the body makes antibodies against its own DNA. It may involve a variety of genes, follow a variety of genetic pathways, and damage a variety of cell types. In many cases, the consequence is impairment of kidney function, which is known as glomerulonephritis.

Immunology research on alveolar lung macrophages wins ASI prize

Erika Duan is a PhD student in the Leukocyte Signalling Laboratory, headed by Associate Professor Margaret Hibbs, studying alveolar lung macrophages. Erika won a prize at the Australasian Society of Immunology (ASI) annual conference in December 2012 for her presentation on how lung macrophages vary with infection and inflammation and the challenges of translating the mouse model data to understanding the human context.