Monash research reveals aspirin is safe for heart surgery patients

Professor Paul Myles, lead author on the
ATACAS study.

A worldwide study led by Monash University clinician-researchers shows that patients who take aspirin before heart surgery are at no greater risk of bleeding or complications. 

Published 25 February in The New England Journal of Medicine, the collaborative research study led by Professor Paul Myles, Head of the Department of Anaesthesia and Perioperative Medicine in the Central Clinical School and Alfred Health, investigated whether stopping or continuing aspirin before coronary artery surgery posed more risks or benefits.

Most patients with coronary artery disease receive aspirin for prevention of heart attack, stroke, and death. However aspirin poses a bleeding risk for patients undergoing surgery, and prior to this study it was unclear whether aspirin should be stopped before coronary artery surgery.

Identification of a mutation in red blood cells that can worsen sickle cell disease

By Dr Jodie Abramovitch

Sickle cell disease (SCD) is a genetic condition in which red blood cells (RBC) have an abnormal bowed or sickle shape due to a mutation of haemoglobin. These RBC are unable to travel well through small blood vessels, often becoming trapped and subsequently dying. This leads to a low red blood cell count (anaemia) which is why this disease can also be known as sickle cell anaemia. The trapped RBC can lead to occlusion of blood vessels leading to lack of oxygen and tissue death in many organ systems - producing extreme pain and organ failure.

L-R: Dr Fiona Brown, Prof. Stephen Jane,
Ms Loretta Cerruti, A/Prof David Curtis

RBC require electrolytes such as potassium (K) and chloride (Cl) to function properly. These electrolytes are actively moved in and out of cells by proteins called co-transporters. The K-Cl co-transporter, therefore, moves K and Cl along with water in and out of RBC to control cell size.

A recent study by researchers from the Australian Centre for Blood Diseases (ACBD), led by Associate Professor David Curtis and Professor Stephen Jane with collaborators from the Florey Institute and Walter and Eliza Hall Institute, identified a mutation within a K-Cl co-transporter known as Kcc1 in a mouse model. This mutation increased the activity of the K-Cl co-transporter leading to smaller RBC.

When the mutation in Kcc1 was introduced into a mouse model of SCD that mimics human disease, it was shown that disease was worsened. A higher proportion of RBC were sickle shaped which led to blocked small blood vessels and more extensive tissue damage. It was concluded that the mutation in Kcc1 was directly linked to a more serious presentation of SCD.

This research highlights the potential therapeutic use of targeting K-Cl (and other electrolyte) co-transporters to inhibit their activity in diseases such as SCD. 

Reference: Brown FC, Conway AJ, Cerruti L, Collinge JE, McLean C, Wiley JS, Kile BT, Jane SM, Curtis DJ. Activation of the erythroid K-Cl cotransporter Kcc1 enhances sickle cell disease pathology in a humanized mouse model. Blood. 2015 Dec:126;2863-70. 

doi: 10.1182/blood-2014-10-609362

Immune system 'patrolling' cells further understood

By Dr Jodie Abramovitch

Within the immune system there are patrolling cells that are constantly scanning the body for signs of infection. They are known as antigen presenting cells. Dendritic cells (DC) are the most efficient example of an antigen presenting cell. When DC find an infection, they are able to alert other cells of the immune system to attack and destroy the infection. Therefore the functions of DC are really important in an effective immune response.

Associate Professor Mark Wright, Head of
the Leucocyte Membrane Protein Group
and senior author of this study

Tetraspanins are a type of protein that are found at the cell surface. Here they bind and bring together (“organise”) other proteins and receptors at the cell surface. CD37 and CD82 are tetraspanins that allow DC to communicate with other immune cells that there is an infection present. CD37 is important for movement of DC to lymph nodes where they find other immune cells. The role of CD82 in DC migration is unclear.

In a recent study published by the Leucocyte Membrane Protein laboratory from the Department of Immunology and Pathology, in collaboration with Melbourne University and international colleagues, the roles of CD37 and CD82 in co-ordinating DC function in response to infection was assessed.

By studying activated DC, it was found that CD82 appeared to have an opposing function to CD37. Whereas CD37 expression was down-regulated following activation of DC, CD82 was up-regulated and restrained DC migration to lymph nodes. DC that were deficient in either CD37 or CD82 were unable to become fully functional and DC that were deficient in CD82 were able to spread much further than CD37 deficient DC. Thus, unactivated DC were observed to have high CD37 expression and low CD82 expression leading to a highly mobile cell that is able to travel easily around the body. Activated DC (DC that have sensed an infection) have low CD37 expression and high CD82 expression which limits mobility of the DC but is able to efficiently signal to immune cells that an infection is present.

This study has detailed a biology of DC that was not previously known and highlights the importance of tetraspanins in coordinating DC function. 

Reference: Jones EL, Wee JL, Demaria MC, Blakeley J, Ho PK, Vega-Ramos J, Villadangos JA, van Spriel AB, Hickey MJ, Hämmerling GJ, Wright MD. Dendritic Cell Migration and Antigen Presentation Are Coordinated by the Opposing Functions of the Tetraspanins CD82 and CD37. J Immunol. 2016 Feb: 196; 978-87. 

doi: 10.4049/jimmunol.1500357

Monash awarded $1.1M grant to support development of revolutionary type of insulin

L-R: Ms Shweta Jagdale (Lab manager) &
Dr Christoph Hagemeyer in the lab

Monash researcher, Dr Christoph Hagemeyer, has received AUD$1.1 million dollars in funding as part of a multi-million dollar collaborative grant to support the development of a revolutionary type of insulin.

The grant is part of a joint research initiative between the JDRF, leading global organisation funding and advocating for type 1 diabetes (T1D) research, and Sanofi US Services Inc., a subsidiary of Sanofi, one of the leading insulin manufacturers and a global pharmaceutical company. The grant will provide up to USD4.6 million to four research projects taking different approaches to developing glucose responsive insulin (GRIs) therapies for treatment of insulin-dependent diabetes.

Dr Hagemeyer, who is a research group leader in the Australian Centre for Blood Diseases, will work in collaboration with Dr Frank Caruso (University of Melbourne), Dr Jonathan Shaw, Dr Mark Copper and Dr Terri Allen (from Baker IDI Heart and Diabetes Institute) to develop glucose-sensing nanoparticles.

Medical student mentoring at Central Clinical School/Alfred Health

by Robert Gillies, Year 5D MBBS student

The Academic Mentor Program is a student-run initiative that was established long before I started studying at Monash. It involves final year medical students volunteering an hour of their time per week to tutor and mentor an assigned group of third year students.

The tutes are unique in that they can be exam-focused, and are peer-driven; so they are less formal and can be more flexible, which facilitates a different kind of learning. Though the tutorials aren't compulsory for third year medical students, I remember them being a great networking opportunity.

 There's so much more than medicine that you can learn from older students - you can learn how to cope with difficult patient interactions, how to balance study and life commitments, about research or extracurricular activities, and everything in between. 

Call for 2017 CCS Honours and Graduate Research projects

AMREP Information Night 2015

The Central Clinical School Student Services Research office is coordinating marketing materials for the 2017 CCS Honours and Graduate Research project index booklet and webpage.  The projects will be advertised for recruitment of students for the following streams:

• Bachelor of Medical Science (Honours)
• Immunology and Human Pathology Honours
• Graduate Research (Masters and PhD)

Staff are asked to submit project information via the MNHS Faculty project database

Perspectives: Call due 26 Feb 2016 for Submissions to the Environment Protection and Biodiversity Conservation Amendment (Prohibition of Live Imports of Primates for Research)

We need monkeys for life saving research to be done.
The Australian capacity to undertake this research is
under threat from a proposed legislative amendment.
Today is the last day you can put in a submission.

.

Now is the time as researchers who use animals in research to make a statement about the significance of animals in research. Animal rights groups generously fill with misinformation the vacuum provided by the normally reticent research community, and are doing their best with Parliamentarians.  They've successfully influenced Senator Rhiannon to make a proposal to prohibit importing non human primates for research. If this amendment is passed, it will mean the inbreeding of Australia's existing research colonies of primates, and ultimately render them useless. It also means that the animal rights groups will use this success for them to lobby more and harder for further erosion of Australia's capacity to conduct medical research using animals.

There is a call for submissions to the Environment Protection and Biodiversity Conservation Amendment (Prohibition of Live Imports of Primates for Research). A senate committee will meet on 1 March to go through the submissions, so today (26 Feb) is the last day you can put your submission in.

See

• Outline of the proposed amendment and all the necessary links to further information, the current submissions and how to make your submission. (Ignore the 18 Jan due date there): www.aph.gov.au/Parliamentary_Business/Committees/Senate/Environment_and_Communications/EPBC_Live_Primates_Bill
• A/Prof James Bourne's 5 Feb video presentation to the Senate committee 
• An excellent University of Edinburgh web page, "Animal Research" for proactive education of the community about their use of animals in research. They are on the front foot!
• 16 Feb 2016 AusSMC Briefing: Do we need to use animals in research? Speakers: Doug Hilton, James Bourne, Malcolm France. Link