Science, Technology and Engineering

27 August 2009
Dear colleagues,

The purpose of this page is to showcase the varied research undertaken by members of the department (or in collaboration with other research groups) that have led to publications in peer-reviewed journals. To highlight your latest publication in this forum, please forward your article details to Molecular Sciences IT Support, together with a short (2-3 sentences) summary for the article. We look forward to your contribution.

For more information, please see Dr Fung Lay.

"publish or perish - publish and flourish"

Journal of Biological Chemistry. 2009 Oct 13. [Epub ahead of print]
This work describes the TRAF2 interaction interface to the cIAPs. Both proteins play important roles in TNF signalling and this discovery enabled an detailed analysis that came up with surprising results; firstly the E3 ligase activity of TRAF2 was not required for TNF induced activation of NF-?B and secondly although TRAF delta RING could rescue NF-?B activation in TRAF2/TRAF5 knock-out cells it was not able to prevent TNF induced cell death. This is the first demonstration that TNF induced NF-?B is insufficient to protect cells from TNF induced death. This paper was the result of an international collaboration between Henning Walczak's lab in Imperial College, London and Catherine Day's lab in Otago, New Zealand. Significantly, part of this manuscript was performed by the second author Delara Pantaki during her Honours year.

(Vince JE, Pantaki D, Feltham R, Mace PD, Cordier SM, Schmuckle AC, Davidson AJ, Callus BA, Wong WW, Gentle IE, Carter H, Lee EF, Walczak H, Day CL, Vaux DL, Silke J)

Virus Research 2009 Sept 26 [Epub ahead of print]
Hepatitis B virus (HBV) is associated with a significant risk of developing hepatocellular carcinoma and this work lexamines cell cycle perturbations induced by HBV. Perturbations in cell cycle may underlie HBV associated liver oncogenic transformation and may help explain the ongoing risk of developing hepatocellular carcinoma. Surprisingly, a  current Honours student from the Department, Aleksandra Bankovaci, is a contributing author, which may be a first in the department! Ueli Nachbur and John Silke from the department are also contributing authors.

(Chin R, Nachbur U , Earnest-Silveira L, Bankovacki A , Koeberlein B, Zentgraf H, Bock CT, Silke J , Torresi J)

Biochemical Pharmacology 2009 Sept 06 [Epub ahead of print]
Michal Ugarenko, Professor Don Phillips and Dr Suzanne Cutts together with collaborators recently published an article entitled "ABT-737 overcomes Bcl-2 mediated resistance to doxorubicin-DNA adducts”.

Doxorubicin is an anthracycline anticancer agent that functions primarily by inhibiting topoisomerase II but also forms covalent DNA adducts depending on the cellular availability of formaldehyde. The small molecule inhibitor, ABT-737, which binds to and inhibits Bcl-2, Bcl-xL and Bcl-w, was used to render previously resistant leukemic cancer cells highly sensitive to doxorubicin–DNA adducts, leading to a classical apoptotic response.

(Ugarenko M, Nudelman A, Rephaeli A, Kimura K, Phillips DR, Cutts SM)

Nucleic Acids Research 2009 Aug 31 [Epub ahead of print]
Dr Benny Evison and Dr Suzanne Cutts together with other lab members and collaborators recently published an article in Nucleic Acids Research entitled "CpG methylation potentiates pixantrone and doxorubicin-induced DNA damage and is a marker of drug sensitivity".

Pixantrone is an anticancer drug that is being considered by the FDA as a new treatment for aggressive non-Hodgkin's lymphoma. This study demonstrates that methylated CpG DNA sequences are preferred sites of DNA damage induced by pixantrone. Cells vastly deficient in DNA methylation displayed resistance to pixantrone, emphasising the importance of this drug target.

(Evison BJ, Bilardi RA, Chiu FC, Pezzoni G, Phillips DR, Cutts SM.)

Nature. 2009 Aug 20;460(7258):1035-9. Epub 2009 Jul 22.
Dr Ueli Nachbur, together with Dr John Silke, contributed to an article in Nature which looked at the role of IAPs in apoptosis pathways.

This research demonstrates that XIAP (X-chromosome linked inhibitor of apoptosis protein) is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.

(Jost PJ, Grabow S, Gray D, McKenzie MD, Nachbur U, Huang DC, Bouillet P, Thomas HE, Borner C, Silke J, Strasser A, Kaufmann T.)

Cell Death Differ. 2009 Aug 14. [Epub ahead of print]
Dr John Silke and R. Brink published a reviewed in Cell Death and Differentiation entitled "Regulation of TNFRSF and innate immune signalling complexes by TRAFs and cIAPs".

There have been a number of recent discoveries relating to the functions of inhibitors of apoptosis (IAPs) and TNF receptor-associated factors (TRAFs) in regulating signalling from TNF receptor superfamily (TNFRSF) members and some tantalizing glimpses into a wider area of influence, that of innate immune signalling. This review describes the role of TRAFs 2 and 3 and cIAPs in regulating TNFRSF signalling, and asks what role IAPs and TRAFs have in innate immune signalling.

(Silke J, Brink R.)

Nature. 2009 Jun 18;459(7249):945-9.
Dr Alex Maier was a co-author on a recent article published in Nature entitled "A newly discovered protein export machine in malaria parasites".

Several hundred malaria parasite proteins are exported beyond an encasing vacuole and into the cytosol of the host erythrocyte, a process that is central to the virulence and viability of the causative Plasmodium species. This research describes a new translocon of exported proteins (PTEX) in Plasmodium falciparum. This translocon offers a new avenue for therapeutic intervention.

(de Koning-Ward TF, Gilson PR, Boddey JA, Rug M, Smith BJ, Papenfuss AT, Sanders PR, Lundie RJ, Maier AG, Cowman AF, Crabb BS.)

Mol Biochem Parasitol. 2009 Aug; 166(2):159-71. Epub 2009 Apr 9.
Dr Christopher Adda and Professor Robin Anders, together with members of the Anders/Foley lab describe the unusual properties of the malaria surface protein, MSP2.

The merozoite surface proein 2 is an intrinsically unstructured protein that is being developed as a malaria vaccine. This research explores the unusual properties of the MSP2, which has been shown to form amyloid-like fibrils that have similar characteristics to other types of amyloid.

(Adda CG, Murphy VJ, Sunde M, Waddington LJ, Schloegel J, Talbo GH, Vingas K, Kienzle V, Masciantonio R, Howlett GJ, Hodder AN, Foley M, Anders RF.)