Newsletter Department of Biochemistry and Molecular Biology

www.med.monash.edu.au/biochem

NEWS AND EVENTS

Issue 46: Jan/Feb 2015

Could our brain instruct our bodies to burn more fat?By uncovering the action of two naturally occurring hormones, scientists may have discovered a way to assist in the shedding of excess fat.

The findings, published in the journal Cell, give new insights into how the brain regulates body fat and may lead to more effective ways to lose weight and prevent obesity by promoting the conversion of white fat to brown fat.

Monash University researchers unravelled a molecular mechanism that depends on the combined action of two hormones - leptin, an appetite suppressant generated in fat cells, and insulin, produced in the pancreas in response to rising levels of glucose in the blood. Their research shows that the two hormones act in concert on a group of neurons in the brain to stimulate the burning of body fat via the nervous system.

Lead researcher Professor Tony Tiganis, from the Department of Biochemistry and Molecular Biology said discovering the combined action of these two hormones could assist in the shedding of excess fat.

Fat in adult humans is typically stored in adipocytes, specialised cells that comprise white fat. But around the neck and shoulders, there is a second form of fat made of brown adipocytes. Rather than storing fat, these cells can be induced to burn it off.

“These hormones give the brain a comprehensive picture of the fatness of the body. Because leptin is produced by fat cells, it measures the level of existing fat reserves - the more fat, the more leptin. Whereas insulin provides a measure of future fat reserves because glucose levels rise when we eat,” Professor Tiganis said.The research team discovered leptin and insulin interact with proopiomelanocortin (POMC) neurons in the brain’s hypothalamus, causing them to send signals through the nervous system promoting the conversion of white fat into brown fat. This leads to burning off of excess fat.

In laboratory work, researchers were able to show that the process is regulated in these neurons by enzymes known as phosphatases, which inhibit the actions of each of the hormones. When the levels of these inhibitors were reduced, the browning and burning of fat increased.

Professor Tiganis said this fundamental process normally serves to maintain body weight but in diet-induced obesity this mechanism goes awry.

“Eventually, we think we may be able to help people lose weight by targeting these two enzymes. Turning white fat into brown fat is a very exciting new approach to developing weight loss agents. But it is not an easy task, and any potential therapy is a long way off,” Professor Tiganis said.

Researchers from the Pennington Biomedical Research Center, the Indiana University School of Medicine, Harvard Medical School and the University of Pennsylvania, USA and the University of Toronto, Canada collaborated on the research.

View the full research paper in Cell: http://www.sciencedirect.com/science/article/pii/S0092867414015931

Page 2Department of Biochemistry and Molecular BiologyNewsletter: Jan/Feb 2015, Issue 46

Message from the Head of Department- Professor Roger DalyDear colleagues,

Well, what a start to 2015. First of all I’d like to congratulate Tony Tiganis and his group for their superb paper in ‘Cell’. This stands as an endorsement of Tony’s belief in tackling important and challenging questions with cutting-edge experimental models, and sets an important benchmark in our pursuit of research excellence. Second, I’d like to welcome two new Lab Heads to the Department, Colby Zaph and Stephen Daley. Colby’s research focuses on how protein methylation by enzymes termed lysine methyltransferases regulates normal development and is dysregulated in disease, while Stephen works on T cell tolerance and how this breaks down as a consequence of inherited mutations. Clearly there is great potential for synergy between their research and that of others in the Department, particularly those working in cancer and immunology. Underpinning our research effort is the unique infrastructure provided at Monash, and a major development in this space is the new Clive and Vera Ramaciotti Centre for Structural Cryo-Electron Microscopy, which opened in February. This centre has at its core the giant Titan Krios electron microscope, which will maintain our capability in molecular imaging at the forefront of international efforts. Finally, as highlighted by Janet Macaulay and Tim Cole in this issue, our undergraduate student numbers increased significantly in 2014, and the trend for an increased intake into BMS and BCH units has continued in 2015. Furthermore, we almost doubled the number of students undertaking Honours studies in the Department in 2015. Clearly, the new year has seen considerable momentum established in both research and education, and I look forward to working with you all throughout the year in order to build on this impressive start.

All the best,

Roger.

Researcher Profile - Dr Garron Dodd (Post-doc in the Tiganis Lab)Growing up in Manchester, England means two things; firstly you inherited an undisputed affinity for a Manchester soccer team (if you’re lucky it’s Manchester United) and secondly you get to grow up in a city brimming with scientific heritage. Manchester boasts several fundamental discoveries from splitting of the atom, the first computer, graphene, the contraceptive pill and in vitro fertilization…so I guess a scientific career seemed inherent!

I got my first taste of science whilst studying for a dual honours degree in Biochemistry and Neuroscience at Keele University, UK. Here I was lucky enough to undertake a fantastic honours project in the laboratory of Dr Stas Glazewski looking at experience-dependent plasticity in cortical neurones. This project was looking at the fundamental mechanisms of learning and ignited my curiosity for neuroscience. By the time I decided to undertake a PhD I was fascinated by how the brain worked and what went wrong in diseases such as obesity and addiction. At the time, one of the most prestigious neuroscience faculties in the UK was headed by Dame Prof Nancy Rothwell and Prof Simon Luckman at the University of Manchester. In order to get my foot in the door I worked as a research technician before embarking on a PhD in the laboratory of Prof Simon Luckman a year later. Here I was given the task of delineating the brain pathways mediating the homeostatic and hedonistic aspects of appetite. Using whole brain fMRI I highlighted that the hedonistic aspects of appetite are mediated by the endocannabinoid system. In terms of anti obesity treatments, targeting the endocannabinoid systems and specifically the antagonism of the CB1 receptor was a hot topic. The heterogeneous expression of the CB1 receptor within the brain meant that CB1 drugs would act on all CB1 receptors with brain, thus eliciting several non-specific effects despite being highly effective at reducing the desire to eat. Whilst in the midst of several projects I serendipitously came across a paper describing the possible existence of an endogenous CB1 antagonist called hemopressin. This was incredibly exciting and I quickly published describing the novel peptide’s anti-obesity actions. Several pharma companies have since taken up the development of hemopressin as an anti-obesity drug but I was able to publish this work in several journals including the Journal of Neuroscience and was awarded the ABTA doctoral researcher of 2012.

During my PhD I became particularly interested in how the brain controls brown adipose tissue and how harnessing the brown adipocyte’s ability to burn fat could combat obesity. It was known that an adipokine called leptin could activate brown adipose tissue via the brain, however the neuronal populations coordinating this response were unknown. To further investigate this I embarked on a postdoctoral position jointly at the University of Manchester, UK and Eli Lilly, USA. With accesses to some fantastic scientists and facilities I discovered that a specific population of neurons in the hypothalamus containing prolactin-releasing peptide, coordinated leptin-induced activation of brown adipose tissue (published in Cell Metabolism).

During this post doc it was becoming apparent that white adipose tissue (WAT) itself could recruit these thermogenic “brown” like or ‘beige’ cells, a processed termed WAT browning. Importantly, stimulating WAT browning prevents diet induced obesity by burning energy. Although little was known of the mechanisms underlying WAT browning, it seemed intuitive that the brain must play a role. With this in mind, in June 2013 I took up a Research fellow position here at Monash University in the laboratory of Prof Tony Tiganis. By working with several talented scientists here at Monash and harnessing the state of the art facilities, we showed that the peripheral hormones leptin and insulin act in synergy on proopiomelanocortin neurons within the brain to initiate WAT browning. This was the first work to truly implement the importance of the brain in the control of WAT browning and defined a novel homeostatic mechanism underlying energy homeostasis (published in Cell, article highlighted in this issue of the Biochemistry newsletter).

Page 3Department of Biochemistry and Molecular BiologyNewsletter: Jan/Feb 2015, Issue 46

Visionary research awarded Cancer Council Victoria funding 89 bold research teams with big ideas applied for funding under the Cancer Council Victoria’s $3 million Venture Grants Scheme – the only one of its kind in Australia. After a rigorous three-month application process, four Victorian research teams with ideas described as “visionary” have begun work to find new treatments for cancer types that are aggressive, difficult to treat or incurable, thanks to financial backing from Cancer Council Victoria donors.Professor Roger Daly, from the Department of Biochemistry and Molecular Biology, will lead a multi-disciplinary team charged with identifying new ways to treat “triple negative breast cancer” (TNBC) – a highly aggressive subtype of the disease that approximately 2000 Australian women are diagnosed with each year. “While it’s becoming increasingly evident that not all TNBCs are the same, we don’t understand the molecular basis of these differences,” Professor Daly said. “We want to figure out ways of personalising treatment to each patient by determining exactly how these cancers differ on a molecular level.”TNBC presents a major clinical problem due to its aggressive nature and because targeted treatments suitable for other forms of breast cancer are ineffective. At the moment the only drug treatment that can be given is chemotherapy, which often has harmful side effects.Cancer cells often exhibit changes in the chemical signals that are transmitted inside the cell, instructing them to grow and divide. These signals are sent by a specific family of protein enzymes termed kinases. The research team hypothesises that there are different subclasses of TNBC, each exhibiting characteristic changes in chemical signals and kinase activity. If this is correct, then measuring these signals and activities represents a novel way of sub-classifying TNBC. If they can identify the kinases in each subclass that generate growth-promoting signals, then these kinases represent potential therapeutic targets, which is a major step towards personalised treatment.To achieve this, they propose to use cutting edge approaches to measure the chemical signals and kinase activi-ties present in TNBCs. In a world first, this will enable them to subclassify the cancers according to the signals that are present, and identify the kinases that emit these sub-class specific signals. This will lead to improved treatments, and ultimately to reductions in morbidity and mortality.

Prof Roger Daly to lead the research team on identifying ways to treat a highly aggressive

subtype of breast cancer.

Cell Signalling and its Therapeutic ImplicationsThe CSTI meeting will be held from 20th May – 22nd May 2015 at Peppers Moonah, Mornington, Victoria.

The CSTI Symposium series has been established as a tribute to the late Associate Professor Martin Lackmann, who tragically and suddenly passed away on 22nd May 2014. The Lackmann Medal for Translational Research will be presented in memory of Prof Martin Lackmann.

The focus of the inaugural CSTI Meeting will be how an increased understanding of aberrant cellular signalling in cancer development and progression can lead to the identification of novel therapeutic strategies and biomarkers.An internationally renowned group of experts from North America, Europe and Australia will speak at what promises to be memorable and rewarding meeting. For a list of confirmed speakers visit http://www.csti.com.au/speakers.htmlRegister now: http://www.csti.com.au/register

For more Biochemistry news and events:please visit our website

www.med.monash.edu.au/biochem

Page 4Newsletter: Jan/Feb 2015, Issue 46 Department of Biochemistry and Molecular Biology

Academia-industry alliance towards autoimmune diseaseMonash University announced on the 12th of January 2015, that it had signed a research collaboration agreement with Janssen-Cilag Pty Ltd. (Janssen), one of the Janssen Pharmaceutical companies of Johnson & Johnson.

The collaboration, facilitated by Johnson & Johnson Innovation, Asia Pacific, will focus on ground-breaking research at Monash University to develop potential new medicines to treat autoimmune diseases and disorders.

The ability of the immune system to discriminate between self and non-self-tissues is a crucial aspect of its function. The failure of some immune cells to appropriately manage this discrimination can result in autoimmunity, which affects millions of people worldwide with diseases such as rheumatoid arthritis, psoriasis and others.

While there are medications on the market that can be used to treat some of these autoimmune diseases, there remains a substantial need for the development of new and improved treatments.

Funding from Janssen will enable Monash University and Janssen immunology scientists to collaboratively research the mechanisms that underlie autoimmune diseases for the development of new and highly innovative potential treatments.

Professor Jamie Rossjohn, from the Department of Biochemistry and Molecular Biology, will lead the research team at Monash University on the three-year research program.

“By understanding the molecular basis for the trigger that causes autoimmune diseases we can uncover opportunities for novel immunotherapeutics,” said Professor Rossjohn.

“Monash University offers us and our partners the world class research facilities, technology, expertise and materials that are all necessary to conduct this level of research. We are excited about the innovative therapeutic solutions that can be developed here at Monash when working with a collaborator like Janssen,” he said.

Prof. Jamie Rossjohn

Did you know that the Library… has a database which gives you access to most ABC & SBS programs, even after they are no longer accessible on ‘Iview’ or ‘On Demand’?

If you have missed a documentary or an episode of something previously aired, you may find it’s available streaming on the database called “Informit EduTV”. This can be located from the Library home page via the “i” databases link.

http://edutv.informit.com.au.ezproxy.lib.monash.edu.au/browse-videos.php

“Informit EduTV” is an online TV streaming resource for Australian tertiary institutions. Informit EduTV makes it easy for lecturers and students to find and instantly watch relevant television content. 10,000 programs including documentaries, drama and series complemented with study guides and articles are accessible via computer, tablet or smartphone.

Features include an Archive of programs from 2006, with up to 80 new programs added weekly; Easy and advanced searching, with programs classified by subject areas; Clip creation and sharing function”. Access requires a Monash Authcate.

Please review the collection for materials of interest and do get in touch if you have any further queries.

Jennifer Kain Subject Librarian Hargrave-Andrew Library - Monash University Ph 9905 2639 Email: jennifer.kain@monash.edu

Notice SOBS Infrastructure Faults and Repairs

ALL equipment repairs, building faults, quote requests, light failures, water leaks, lab coats, access requests, in fact anything and everything, apart from a genuine emergency, should be logged using this site:https://sites.google.com/a/monash.edu/sobs-equipment-repairs/

Page 5Department of Biochemistry and Molecular BiologyNewsletter: Jan/Feb 2015, Issue 46

The Biochemistry Imaging Facility has new equipmentThe Biochemistry Imaging Facility (http://www.med.monash.edu.au/biochem/imaging-facility/) has exciting new equipment available for use now.1. Biochem Qiagen plaform; From nucleic acid extraction, to quantification, to automated pipetting for real time PCR.All chemistries and consumables for the equipment listed are immediately available from the Imaging Facility manager upon email request.

QIAcube HTAutomated mid-high throughput nucleic acid purification in 96-well format using silica membrane technology. Users can quickly and easily purify DNA, RNA, and miRNA from almost any type of sample — including cells, tissues as well as from bacteria and viruses in animal samples. Automated protocols and dedicated QIAcube HT purification kits and plasticware are readily available now.

QIAxpertQIAxpert is an innovative high-speed microfluidic UV/VIS spectrophotometer which profiles sample content to differentiate between DNA and RNA and sample impurities. It is fast and easy to use, analyzing up to 15 samples within 2 minutes — just pipet samples onto the QIAxpert slide, place it into the reader, and select the pre-programmed method on the integrated touchscreen.

QIA RGQ-5 Plex + HRMReal time PCR instrument in rotary format (72 and 100 tubes rotors), 5 channel (green, yellow, orange, red, crimson) and High Resolution Melt analyser with free analysis software. Chemistries and plastic ware available as needed.

QIA robot (CAS-1200)automated pipetting for setting up assays such as real time PCR. 1 – 200ul pipetting. Tips box on hand as per request.

2. Biochem Biorad platformBiorad CFX384 Touch384 well plate format real time PCRBiorad Chemi TouchSensitive system which replaces the use of Xray film/developers. Captures Chemiluminescence digitally and creates a tiff file for analysis. Software analysis software copies are free to all users.

Education Undergraduate 2014

Undergraduate student numbers increased significantly in 2014. There was an increased demand and resultant number of students enrolled in the first year of the Bachelor of Biomedical Science (>40% increase to 460 students). This resulted in part due to the new pathway into the Monash postgraduate Medical (MBBS) program which guarantees that at least 50 of the 75 places available into the Graduate Entry MBBS, will be reserved for students who have completed the Monash Bachelor of Biomedical Science (http://med.monash.edu.au/medical/gippsland/mbbs-pathways.html). We also had an increased number of students completing BCH2011 (423) and BCH2022 (220). These units make up the Biochemistry minor and major within the BSc – hence an increase in these numbers bodes well for increased 3rd year and Honours enrollments. The increased student numbers however increase the number of tutors/demonstrators required – so please encourage your PhD students to participate. Tutoring/demonstrating is a great way for PhD students to earn some money and also provides them with valuable experiences and increases and broadens their basic biochemistry and molecular biology.

The Departmental education committee met in December 2014 to commence the process of reviewing our current offerings in the BSc. The aim is to ensure that we are offering a relevant and contemporary program of study to our students. This project will be ongoing in 2015 and if you are interested in being involved please contact Janet Macaulay (janet.macaulay@monash.edu).

Honours 2015

27 enthusiastic Honours students started their studies last week in the Department to join two mid-year students at their half-way mark. We have students from BMS, Science, Biotechnology and Masters Biomed Part 1 making up the Honours group and they will begin with some coursework studies soon and start to find their way in the lab with their research projects. We enjoyed a sunny day for the Honours Welcome BBQ on Feb 27th with about 100 people from the Department. The raffle draw was a highlight and Roger Daly presented our top 2014 Honours student, Samuel Rodgers with the 2014 Honours Stuart Stone Medal and a cheque for $500 (see right). This should be a good enticement for our 2015 Honours group! Please make our new Honours students feel welcome to the Department.

Environmental Sustainability At MonashAnyone concerned with any environmental issues should contact

Shani Keleher (shani.keleher@monash.edu) or visit The Office of Environmental Sustainability (TOES)

http://www.fsd.monash.edu.au/environmental-sustainability.

Page 6Department of Biochemistry and Molecular BiologyNewsletter: Jan/Feb 2015, Issue 46

POSTGRADUATE MATTERS PhD GraduatesHenna Veera KuusistoThesis: “Altered Nuclear Transport in Transformed Cells” Supervisor: Prof David Jans Linda Wiltzer Thesis: “Lyssavirus P-protein interactions with STATs- roles in immune evasion and disease, and potential for therapeutic targeting” Supervisors: Prof David Jans, Dr Gregory Moseley

All queries on Postgraduate matters: Please contact Prof Mibel Aguilar mibel.aguilar@monash.edu

NOTDRSAre you interested in getting to know other postgraduate students and venturing outside the lab from time to time? NOTDRS are currently recruiting new committee members for 2015. If you, or anyone you know, are interested in helping organise and run social events including “Escape the Lab”, Lasertag and the Melbourne Cup BBQ, please contact one of the committee members or drop by our Facebook page (https://www.facebook.com/groups/NOTDRS/). Also, look out for our Annual General Meeting (AGM) in March 2015!

On behalf of the NOTDRS committee,Matt Eramo(matthew.eramo@monash.edu)

OH&S in the new yearUpdated Monash Biochem Safety Induction forms for 2015 are now available from the safety officer. Ensure all new staff, students, visitors, collaborators etc who will be working to any capacity in the labs/offices here in Biochem to have these documents completed especially before commencing any lab work. All those who will not have a Monash Authcate username/password issued to them, they can forgo the Monash Online component.Your training records now appear in SAP/ESS. Check that your personal training records are up to date and have not lapsed. If your records are not correct or missing recently completed training sessions, feel free to email me your details so I can chase it up.If you had completed the Monash Online Safety Induction >3 years ago, your records will be now showing as either ‘not completed’ or ‘expired’ or ‘lapsed’ or ‘overdue’, you will be required to complete this ASAP as stipulated by Monash University OHS policy. Most courses are now required to be completed every three years.Click on this link to complete the Monash Online Safety Induction:www.monash.edu.au/ohs/training/safety-induction-program.html • duration: Allow 30 minutes • valid for three yearsThere are another three compulsory components which were introduced last year, if you haven’t completed these as yet, here are the links (we all need to do these): • Ethical and Professional Conduct o duration: Allow 20 minutes o valid for three years • Privacy o duration: Allow 20 minutes o valid for three years • Equal Opportunity o duration: Allow 20 minutes (Important: Please type in the relevant enrolment key on the Equal Opportunity web page when self enrolling for this course. Do not use copy and paste for enrolment key) o valid for two yearsLink to MBio e-bulletin:

www.med.monash.edu.au/mbio-gradschool/e-bulletin.html

If you are a First Aider, Floor Warden or any other OHS role......and wish to update your training, please contact Irene Hatzinisiriou (irene.hatzinisiriou@monash.edu) so she can give you the appropriate cost centre/fund number, as these are subsidised by the university and not by the department.All other trainings are the responsibility of the Supervisor/lab group as they are related to your lab/office work.

CONTACT US: Department of Biochemistry and Molecular Biology Monash University, Ground Floor, Building 77, Wellington Road, Clayton VIC 3800 Australia Website: www.med.monash.edu.au/biochem Tel: +61 3 990 29400 Fax: +61 3 990 29500