newsletter department of biochemistry and molecular biology · · 2013-09-17newsletter department...

Newsletter Department of Biochemistry and Molecular Biology

www.med.monash.edu.au/biochem

NEWS AND EVENTS

Issue 37: August 2013

CongratulationsDear colleagues,

On behalf of the Department I would like to extend my congratulations to Prof Jamie Rossjohn, who along with Professor James McCluskey and Dr Lars Kjer-Nielsen (University of Melbourne) was awarded the UNSW Eureka Prize for scientific research. All of us involved in research strive for the Eureka moment, and Jamie, his team and collaborators certainly achieved this with their discovery that molecules produced when bacteria metabolize certain B vitamins can activate a class of immune T cell called mucosa-associated invariant T (MAIT) cells. This has major clinical implications, for example in the development of novel therapeutic approaches against particular pathogens or in the treatment of immunodeficiencies. The award of this prize is an outstanding achievement and gives appropriate recognition for the stellar work consistently undertaken by the Rossjohn lab.

Roger.

(Prof Roger Daly, Head of Department)

Professor Jamie Rossjohn, from the School of Biomedical Sciences’ Department of Biochemistry and Molecular Biology, together with Professors James McCluskey and Lars Kjer-Nielsen from the University of Melbourne took out the 2013 University of New South Wales Eureka Prize for Scientific Research.

The team uncovered what activates a widespread, but, until recently, mysterious gut-dwelling immune cell. They noticed that a protein from these cells only formed properly in the presence of by-products of vitamin B, which are formed by invasive bacteria and yeast. It became clear that these vitamin B metabolites were providing early warning to our immune system.

The research opens up new opportunities to understand the role of the ‘microbiota’ in our gut in regulating human health and disease. It could lead to vaccine development and other therapies for a range of infections from thrush to TB.

“The utter brilliance of Lars Kjer-Nielsen’s observations, combined with the strong teamwork of the Rossjohn and McCluskey labs, and key contributions from Australia-wide collaborators, have led to this Australian-centric discovery. A discovery that we hope will, ultimately, improve and save the lives of millions of people worldwide,” Professor Rossjohn said.

Extracted from article Eureka! Monash scientists take home two prizes, 5th September http://monash.edu/news/show/eureka-monash-scientists-take-home-two-prizes

Department webpageOur webpage has been re-designed: http://www.med.monash.edu.au/biochem/

Please send feedback to [email protected] and [email protected]

First Eureka Prize for the Department

Newsletter: August 2013, Issue 37 Department of Biochemistry and Molecular Biology

Update from the Head of Department, Prof Roger DalyProf Daly will be sending a message to the Department each month in the newsletter.

the new EM facility has begun, and the University has ordered two new microscopes. One of these will be a Titan Krios equipped with the Falcon II camera system, providing world leading imaging capability. In the case of network biology, I’ve established an international search committee featuring three world leaders in computational/systems biology who will assist us with recruitment of a stellar group leader. In addition, an exciting candidate in the area of cancer cell biology is visiting and presenting in early October – keep an eye open for this seminar.

Obviously recruitment isn’t the only process that we need to consider as we plan for the future, and so the Department will be holding a Strategic Planning Retreat in mid-November, involving all of the group heads and senior academic staff.

This will involve four sessions centred on research areas/themes important for our development – molecular imaging, cellular imaging, network biology and multidisciplinary research – as well as sessions on other key strategic issues. The latter have been drawn from my earlier ‘one-on-one’ discussions with the group heads, and include mentorship/staff development, communication and connectivity, research funding and commercialization, and the research/education interface. In order to highlight some of the research themes, we’ve invited external speakers with internationally-recognized expertise – these include Kat Gaus (University of NSW), David James (Garvan Institute), Kaylene Simpson (Peter MacCallum Cancer Institute) and Nic Nicola (WEHI). These speakers will also stay throughout the meeting and provide input to the discussions. With regard to the other strategic issues, working groups will be established to research their designated areas and report back at the retreat, providing a platform for further discussion. Finally, it is of course critical that this retreat leads to solid recommendations that are implemented as we move forward, and the working groups will provide a potential mechanism for driving such implementation and achieving positive outcomes.

I felt incredibly honored to be appointed as the new Head of Department earlier this year, as this is the largest and leading Department in its discipline in Australia. My goal now is to drive its future development so that it is widely recognized as one of the leading Biochemistry Departments internationally. One key area critical for this will be recruitment of new group leaders. My view is that future recruitment into the Department should be done in a strategic manner, with the goal of either maintaining our competitive edge in particular areas, or synergistically building strength in research themes where we already have a strong foundation. Two areas that I believe are critical for our further development are molecular imaging, representing the interface between structural biology and high resolution imaging, and computational network biology, involving functional analysis at a network, rather than the single molecule, level. With regard to the former, the University is currently attempting to recruit a Scientific Director for the Cryo-Electron Microscopy Platform established by James Whisstock and Ian Smith. In addition, construction of

POSTGRADUATE MATTERSPhD Graduates Thesis: “Structural insights into the recognition of CD1d-restricted self antigens by the Natural Killer T cell T cell antigen Receptor” Supervisors: Jamie Rossjohn / Alan Riboldi-Tunnicliffe

Tasha Mendes Thesis: “Functional characterisation of the RIO kinase family” Supervisor: Peter Boag Queries on Postgraduate matters Please contact Prof Mibel Aguilar

Andrew Clarke

Link to MBio e-bulletin: www.med.monash.edu.au/mbio-gradschool/e-bulletin.html

Department of Biochemistry and Molecular BiologyNewsletter: August 2013, Issue 37

From little things, big things growSupramolecular Self-Assembly of β-Peptides Leads to Fibre Formation

Supramolecular self-assembly represents a powerful approach to the design of functional nanomaterials. Peptide self-assembled systems offer significant advantages including biological compatibility, ease of synthesis, low toxicity and functionalisability. However, the control over essential features such as chemical, structural and metabolic stability, the scale and relatively slow rate of self-assembly remain significant challenges.

In a collaboration between the Biochemistry (Mark Delborgo and Mibel Aguilar, together with Matthew Wilce, Jackie Wilce and Daouda Traore) and Chemistry Departments (Patrick Perlmutter, Craig Forsyth) and LaTrobe University (Adam Mechler), a completely new approach to peptide fibres has been developed, that has just been published in Angewandte Chemie International Edition (IF 13.734).

They have designed helical N-acetyl-β3-peptides that spontaneously self-assemble to form fibres ranging in size from nano- to macro-scale. The peptide monomers self-assemble in a unique head-to-tail fashion which is driven by a 3-point H-bond motif associated with the 14-helical structure of N-acetyl-β3-peptides.

This provides extraordinary opportunities for designing new materials with functionality located along these faces. Perhaps even more significant, is that the perfect pitch offers the opportunity to design a supramolecular self-assembly motif to link the monomers in a highly symmetrical manner reminiscent of one dimensional crystallization. The inherent flexibility, as well as ease of synthesis, provides new avenues for the development of novel nanomaterials.

Del Borgo MP, Mechler* AI, Traore D, Forsyth C, Wilce JA, Wilce MCJ, Aguilar* MI and Perlmutter* P, ‘Supramolecular Self-Assembly of N-Acetyl capped β-Peptides Leads to Nano-to Macroscale Fibre Formation’. Angewandte Chemie Int Ed. 2013, 52, 8266-8270. DOI: 10.1002/anie. Selected for Fronticepiece Highlights

Article courtesy of Prof Mibel Aguilar

Department of Biochemistry and Molecular Biology

Lab Head Profile: Dr Faselli CoulibalyI always knew I was going to come to New Zealand and Australia… only I thought it would be with a French rugby jersey rather than a lab coat. Research brought me here and I have now been almost 10 years in the Southern Hemisphere.

My first taste of research dates back from 1998 as part of a double MSc degree in Chemistry (Montpellier, France) and Biotechnologies (Bristol, UK). I was able to fulfil one of my long-time dreams for my MSc internship: to join the Pasteur Institute in Paris; home of Louis Pasteur himself, Jacques Monod, Luc Montagnier… There I was fortunate to meet Marie Flamand, a molecular virologist with a contagious passion for emerging viruses, who offered me a position in the Arbovirus and Haemorrhagic Fever unit despite my total lack of lab experience. This was the time when Ebola virus re-emerged in central Africa. The Pasteur Institute was in the spotlight for Bernard Le Guenno’s work on the origin of the virus and a brand new Biosafety level 4 laboratory in Lyon expanded its research capacity on haemorrhagic fevers. Thus, I was already seeing myself travelling across Africa to chase these viruses. But, of course, the biochemist that I was got assigned to a structural biology project rather than Dustin Hoffman’s role in Outbreak. It seemed that my most exciting prospect was going to be growing dengue in a Biosafety Level 3 lab. As disappointed as I was, this was probably the turn of my career and led me to engage in research that would allow me to see virus so much closer than if I had travelled the world to chase them!

Newsletter: August 2013, Issue 37

The initial project at Pasteur was carried in collaboration with Felix Rey, a young group leader at the French CNRS returning from Steve Harrison’s laboratory at Harvard Medical School. In a few years, Felix had single-handedly created a world-leading laboratory achieving a true convergence between a profound understanding of the virus world and excellence in X-ray crystallography. In 1999, I started a PhD with Felix on the study of the infectious particles of birnaviruses, emerging pathogens of poultry and salmon. After consulting with Jorge Navaza, the guru of molecular replacement and inventor of AMoRe, and harassing our electron microscopist Jean Lepault, I was able to solve what turned out to be first structure of an icosahedral particle determined in France. The birnavirus structure revealed a unique architecture that radically changed our view of the biology of this viral family. Beyond, it suggested a bold evolutionary scenario linking complex RNA viruses such as human rotavirus to simple insect viruses. Up until now, the discovery of “my” virus on the cover of Cell remains the most rewarding moment of my scientific path.

In 2004, I took a research fellow position at the University of Auckland to join Ted Baker’s laboratory. This choice certainly departed from the classical career path in France… .I never regretted this decision from a personal or professional point of view. In Ted Baker’s laboratory, I initiated work on poxvirus assembly and virulence that I pursue here at Monash University, and contributed to the study of Streptoccus pyogenes pili. These hair-like appendages had only been discovered recently in Gram-positive bacteria and represented an attractive vaccine target for common human diseases. This work primarily carried out by an outstanding PhD student, HaeJoo Kang, resulted in the first structural characterization of a Gram-positive bacterial pilin. This research opened a new field of research that focuses on stabilizing isopeptide bonds, a previously overlooked feature predicted to exist in hundreds of bacterial surface proteins (Science, 07).

At the same time, Peter Metcalf had another challenge for me where he was trying to determine the structure of the smallest crystals analysed by X-ray crystallography. These infectious crystals called polyhedra are common in insect viruses but were largely uncharacterized because of their extremely small size. Intense research allowed us to push the boundary of X-ray microcrystallography and determine the structure of cypovirus polyhedra directly purified from infected insects (Nature, 07). While at Monash already and still in collaboration with Peter, I determined the structure of the second class of polyhedra suggesting evolutionary convergence between polyhedra of RNA and DNA viruses (PNAS, 09). Comparative analysis revealed common molecular characteristics that may explain the propensity of these proteins to crystallise in vivo, an attractive feature in view of protein crystallization for structural studies.

In 2007, I attended the Lorne Conference and the meeting of the Australasian Virology society. I received the Young Investigator and the Excellence awards respectively; and thought that Australia seemed like a motivating place to work! A visit of Jamie Rossjohn’s laboratory finally convinced me to join the Biochemistry Department at Monash University to establish a research group. While this really was a group of one for the first six months, I benefited from a strong level of support in those critical years from fellow structural biologists but also at a Departmental level from Rob Pike and a University level as part of the Monash Research Accelerator Program. With the award of an NHMRC CDA in my first year at Monash, I could steadily expand my group over the next 4 years with project funding from the NHMRC and ARC. In addition, three grants from the Gates Foundation supported the development of a new project aiming to design ultra-stable microcapsules for HIV and flu vaccination based on viral polyhedra.

As an ARC Future Fellow (2013-16), my research now focuses on very diverse systems within the virosphere such as poxvirus-directed remodelling of host membranes; the recognition and invasion of target cells by the Hepatitis C virus; and the architecture of the replication machinery of Hendra virus. These have in common a lack of structural information hindering the establishment of a solid paradigm for these complex processes. To address ever more complex questions, I am also interested by the development of novel and hybrid methods in structural biology including X-ray microcrystallography, electron microscopy and NMR.

Whether these methods will be supplanted by the much hyped free-electron lasers remains to be seen but I bet that, once again, viruses will be the ideal tools to establish and push the limits of structural biology… and I’ll surely want to be around!


RECENT MEMBERS OF STAFF

Lab Head New Staff Member Position

Anthony Purcell Patricia Illing Research Fellow

Jamie Rossjohn Eric Chabrol Research Fellow

Ana Traven Tara Quenault Affiliate

Jackie Wilce Kieran Rimmer Research Fellow


SeminarWednesday September 18th

Minna-liisa Anko (WEHI)

Functional role of RNA-protein interactions in cells

****************

4 pm in Lecture Theatre M2 (Building 13)

Food and drink will follow the seminar in the foyer of building 76/77

Suggestions for future speakers can be sent to committee members Martin Stone, Travis Beddoe, Ana Traven or Peter Boag

For more Biochemistry news, please visit our website www.med.monash.edu.au/biochem

OHS: SYRINGE USE IN THE LABSIn the last several years there have been numerous injuries resulting from the use of ‘male’ (barrel) fitting syringes in our Department. At a 2008 Departmental OHS meeting it was decided unanimously that ‘male’ fitting syringes should be avoided wherever possible, as they are not safe for the user.

The Department’s STRONGEST RECOMMENDATION is that all labs use the ‘female’ fitting syringes that screw on to avoid unnecessary and often serious injuries.

The Department recommends that all labs throw out or hand back unopened/unused boxes to the store and restock with the safer alternatives.

Even though the Store stocks the male fitting syringes, you should avoid ordering these.

If you use the male-ended instead of the recommended female ended syringe, you MUST have a risk assessment in place (this should be approved by your Supervisor).


OHS MATTERS

Are you aware that NOT ALL SOLUTIONS can be heated in a microwave oven???? CHECK YOUR MSDS FIRST

Have you been trained to use a ‘Laboratory’ Microwave Oven?

Have you read your protocol and procedure carefully before using the microwave oven?

Is there an associated risk assessment for what you are using the microwave oven for?

Have you read it and signed a form in your lab for safe working procedures?

If you come into contact (face, eyes, skin, clothes) with the hot solution, do you know what to do?

This is what you will need to safely use a lab microwave oven: ● SAFETY GLASSES ● LAB COAT FULLY BUTTONED ● CLOSED SHOES ● HEAT PROTECTION GLOVES

DO NOT cover or seal your container/flask/bottle in a microwave oven.

DO NOT walk away while heating your solution.

Wait a few seconds before removing from oven.

DO NOT over heat your solution.

Gas cylindersIf anyone wants to handle/transport/change a gas cylinder of any size or a gas valve, tubing on a gas cylinder MUST have completed a GAS CYLINDER TRAINING SESSION ACCREDITED BY MONASH OHS. Please avoid handling or changing gas cylinders if you have not received this training. We’ve had inexperienced people damaging gas cylinders which has posed a threat to people’s safety in the lab. If a gas cylinder is hissing, please do not ignore but do contact a trained gas cylinder user!!! See your Safety Officer for training.

Using microwave ovens in the lab

QUICK OVERVIEW OF WHAT TO DO WHEN AN EMERGENCY ARISES:

1. Remain CALM…

2. Yell out for a First Aider (don’t go looking for one yourself, get someone else to go looking)

3. First Aiders: Read MSDS before treating any chemical injury

4. First Aiders: Call Med Centre if necessary ext. 53175

5. First Aiders: Call the Safety Officer and/or Safety Representative as soon as possible



RECENT PUBLICATIONS


BIOCHEMISTRY RESESARCH PUBLICATIONSfor AUGUST 2013

1. Al-Musawi, S.L., K.L. Walton, D. Heath, C.M. Simpson, and C.A. Harrison, Species differences in the expression and activity of bone morphogenetic protein 15. Endocrinology, 2013. 154(2): p. 888-899

2. Brice, A. and G.W. Moseley, REVIEW: Viral interactions with microtubules: orchestrators of host cell biology? Future Virol, 2013. 8(3): p. 229-243

3. Chan, A.L., T. Grossman, V. Zuckerman, D. Campigli Di Giammartino, O. Moshel, M. Scheffner, B. Monahan, P. Pilling, Y.H. Jiang, S. Haupt, O. Schueler-Furman, and Y. Haupt, c-Abl phosphorylates E6AP and regulates its E3 ubiquitin ligase activity. Biochemistry, 2013. 52(18): p. 3119-3129

4. Chang, F.T., J.D. McGhie, F.L. Chan, M.C. Tang, M.A. Anderson, J.R. Mann, K.H. Andy Choo, and L.H. Wong, PML bodies provide an important platform for the maintenance of telomeric chromatin integrity in embryonic stem cells. Nucleic Acids Res, 2013. 41(8): p. 4447-4458

5. Cheung, V., S. Bouralexis, and M.T. Gillespie, PTHrP Overexpression Increases Sensitivity of Breast Cancer Cells to Apo2L/TRAIL. PLoS One, 2013. 8(6): p. e66343.1-11

6. Foijer, F., T. DiTommaso, G. Donati, K. Hautaviita, S.Z. Xie, E. Heath, I. Smyth, F.M. Watt, P.K. Sorger, and A. Bradley, Spindle checkpoint deficiency is tolerated by murine epidermal cells but not hair follicle stem cells. Proc Natl Acad Sci U S A, 2013. 110(8): p. 2928-2933 [BCH,ANT]

7. Hargreaves, C.E., M. Grasso, C.S. Hampe, A. Stenkova, S. Atkinson, G.W. Joshua, B.W. Wren, A.M. Buckle, D. Dunn-Walters, and J.P. Banga, Yersinia enterocolitica provides the link between thyroid-stimulating antibodies and their germline counterparts in Graves’ disease. J Immunol, 2013. 190(11): p. 5373-5381

8. Haupt, S., C. Mitchell, V. Corneille, J. Shortt, S. Fox, P.P. Pandolfi, M. Castillo-Martin, D.M. Bonal, C. Cordon-Cardo, G. Lozano, and Y. Haupt, Loss of PML cooperates with mutant p53 to drive more aggressive cancers in a gender-dependent manner. Cell Cycle, 2013. 12(11): p. 1722-1731

9. Hu, M., S.A. Crawford, D.C. Henstridge, I.H. Ng, E.J. Boey, Y. Xu, M.A. Febbraio, D.A. Jans, and M.A. Bogoyevitch, p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival. Biochem J, 2013. 453(3): p. 381-391

10. Khor, R., W.K. Yip, M. Bressel, W. Rose, G. Duchesne, and F. Foroudi, Practical implementation of an existing smoking detection pipeline and reduced support vector machine training corpus requirements. J Am Med Inform Assoc, 2013. E-pub

11. Layton, D., C. Laverty, and E.C. Nice, REVIEW: Design and operation of an automated high-throughput monoclonal antibody facility. Biophys Rev, 2013. 5: p. 47-55

12. Marchesan, S., Y. Qu, L.J. Waddington, C.D. Easton, V. Glattauer, T.J. Lithgow, K.M. McLean, J.S. Forsythe, and P.G. Hartley, Self-assembly of ciprofloxacin and a tripeptide into an antimicrobial nanostructured hydrogel. Biomaterials, 2013. 34(14): p. 3678-3687

13. Miyamoto, Y., M.A. Baker, P.A. Whiley, A. Arjomand, J. Ludeman, C. Wong, D.A. Jans, and K.L. Loveland, Towards delineation of a developmental alpha-importome in the mammalian male germline. Biochim Biophys Acta, 2013. 1833(3): p. 731-742 [BCH,ANT]

14. Muscat, G.E., N.A. Eriksson, K. Byth, S. Loi, D. Graham, S. Jindal, M.J. Davis, C. Clyne, J.W. Funder, E.R. Simpson, M.A. Ragan, E. Kuczek, P.J. Fuller, W.D. Tilley, P.J. Leedman, and C.L. Clarke, Research resource: nuclear receptors as transcriptome: discriminant and prognostic value in breast cancer. Mol Endocrinol, 2013. 27(2): p. 350-365

15. Niclis, J.C., A. Pinar, J.M. Haynes, W. Alsanie, R. Jenny, M. Dottori, and D.S. Cram, Characterization of forebrain neurons derived from late-onset Huntington’s disease human embryonic stem cell lines. Front Cell Neurosci, 2013. 7(37): p. 1-13 [BCH,ANT,ARMI]


RECENT PUBLICATIONS continued

16. Sivagurunathan, S., C.N. Pagel, L.H. Loh, L.C. Wijeyewickrema, R.N. Pike, and E.J. Mackie, Thrombin inhibits osteoclast differentiation through a non-proteolytic mechanism. J Mol Endocrinol, 2013. 50(3): p. 347-359

17. Tamura, Y., Y. Harada, S. Nishikawa, K. Yamano, M. Kamiya, T. Shiota, T. Kuroda, O. Kuge, H. Sesaki, K. Imai, K. Tomii, and T. Endo, Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria. Cell Metab, 2013. 17(5): p. 709-718

18. To, S.Q., K.C. Knower, and C.D. Clyne, REVIEW: Origins and Actions of Tumor Necrosis Factor alpha in Postmenopausal Breast Cancer. J Interferon Cytokine Res, 2013. 33(7): p. 335-345

19. Wong, A., D.R. Grubb, N. Cooley, J. Luo, and E.A. Woodcock, Regulation of autophagy in cardiomyocytes by Ins(1,4,5)P(3) and IP(3)-receptors. J Mol Cell Cardiol, 2013. 54: p. 19-24

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 Content and Layout: [email protected] Photography: MNHS Multimedia Services


newsletter department of biochemistry and molecular biology · · 2013-09-17newsletter department...

Documents