News

New Co-Author Publication! Ensa controls S-phase length by modulating Treslin levels.

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Great news, we have published a co-authored paper entitled ‘Ensa controls S-phase length by modulating Treslin levels’ in the prestigious journal ‘Nature Communications’. This work was started back in 2011 when I was a Post-Doc in the laboratory of Anna Castro in France. It’s exciting to see those inital discoveries transition into the finished paper.
The article is Open Access and free to download, which you can do so here: http://www.nature.com/articles/s41467-017-00339-4

 

ABSTRACT

The Greatwall/Ensa/PP2A-B55 pathway is essential for controlling mitotic substrate phos- phorylation and mitotic entry. Here, we investigate the effect of the knockdown of the Gwl substrate, Ensa, in human cells. Unexpectedly, Ensa knockdown promotes a dramatic extension of S phase associated with a lowered density of replication forks. Notably, Ensa depletion results in a decrease of Treslin levels, a pivotal protein for the firing of replication origins. Accordingly, the extended S phase in Ensa-depleted cells is completely rescued by the overexpression of Treslin. Our data herein reveal a new mechanism by which normal cells regulate S-phase duration by controlling the ubiquitin-proteasome degradation of Treslin in a Gwl/Ensa-dependent pathway.

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New Publication in Cell! The Phosphoregulation of Mitosis

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We are incredibly excited to announce that our SnapShot is out today in Cell!
This snapshot of mitosis collates hundreds of phosphorylation events and directly links them with their regulatory kinases and counterbalancing phosphatases, in both time and space, in a highly innovative ‘circtanglar’ cell layout. More importantly, the static PDF version is accompanied by an interactive website that enables users to access direct links to PubMed, UniProt, and Aquaria 3D protein structures for each and every phosphorylation event shown. The pop-up boxes also contain over 100 additional phosphorylation sites on dozens of proteins essential for mitosis. You can access the interactive web version here:  http://www.cell.com/cell/enhanced/odonoghue2
Even better news is that until August 04, 2017 the PDF version of the SnapShot is freely accessible for everyone at the following link https://authors.elsevier.com/a/1VDWh_278yyILK
A big thank-you to Jenny, Sam, Marcos and Sean for helping me put together what I hope will be an amazing resource for anyone interested in how cells divide and phosphorylation in general.

New Publication: Hedgehog signaling in small cell lung cancer

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Great news we have a new co-author publication in Oncogene!

This work was in collaboration with Prof. Neil Wakins here at the Garvan Institute and focuses on the role of Hedgehog (Hh)  signaling in small cell lung cancer (SCLC). Small cell lung cancer is a common, aggressive malignancy with universally poor prognosis.

Full details can be found here [link]

TITLE: “The role of canonical and non-canonical Hedgehog signaling in tumor progression in a mouse model of small cell lung cancer”

ABSTRACT:

Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that Hh inhibitors block the self-renewal capacity of SCLC cells, the lack of activating pathway mutations have cast doubt over the significance of these observations. In particular, the existence of autocrine, ligand-dependent Hh signaling in SCLC has been disputed. In a conditional Tp53;Rb1 mutant mouse model of SCLC, we now demonstrate a requirement for the Hh ligand Sonic Hedgehog (Shh) for the progression of SCLC. Conversely, we show that conditional Shh overexpression activates canonical Hh signaling in SCLC cells, and markedly accelerates tumor progression. When compared to mouse SCLC tumors expressing an activating, ligand-independent Smo mutant, tumors overexpressing Shh exhibited marked chromosomal instability and Smoothened-independent upregulation of Cyclin B1, a putative non-canonical arm of the Hh pathway. In turn, we show that overexpression of Cyclin B1 induces chromosomal instability in mouse embryonic fibroblasts lacking both Tp53 and Rb1. These results provide strong support for an autocrine, ligand-dependent model of Hh signaling in SCLC pathogenesis, and reveal a novel role for non-canonical Hh signaling through the induction of chromosomal instability.

 

New Co-Author Publication – Attacking the tissue around Pancreatic Cancer

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It was a great pleasure to be apart of this amazing research by Claire Venin and Paul Timpson, which was recently published in Science Translational Medicine, one of the very best journals in the world.

Here is a brief intro into the research.

ROCK-ing pancreatic cancer to the core

Pancreatic cancer, one of the most deadly and difficult-to-treat tumor types in patients, usually has a dense stroma that can be difficult for drugs to penetrate. Stromal characteristics can also affect multiple other aspects of tumor biology, including metastatic spread, vascular supply, and immune response. Vennin et al. used Fasudil, a drug that inhibits a protein called ROCK and is already used for some conditions in people, to demonstrate the feasibility including short-term tumor stroma remodeling as part of cancer treatment. In genetically engineered and patient-derived mouse models of pancreatic cancer, priming with Fasudil disrupted the tumors’ extracellular matrix and improved the effectiveness of subsequent treatment with standard-of-care chemotherapy for this disease.

If you would like to know more you can read the full article here:
Vennin, C. et al. 2017. Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Science translational medicine. 9, 384 (Apr. 2017).

New Review Published “The role of MDM2 and MDM4 in breast cancer development and prevention”

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jmcb

Great news, we have had a co-author review published in the Journal of Molecular and Cellular Biology.

You can check out the full review here.

Abstract

The major cause of death from breast cancer is not the primary tumour, but relapsing, drug-resistant, metastatic disease. Identifying factors that contribute to aggressive cancer offers important leads for therapy. Inherent defense against carcinogens depends on the individual molecular make-up of each person. Important molecular determinants of these responses are under the control of the mouse double minute (MDM) family: comprised of the proteins MDM2 and MDM4. In normal, healthy adult cells, the MDM family functions to critically regulate measured, cellular responses to stress and subsequent recovery. Proper function of the MDM family is vital for normal breast development, but also for preserving genomic fidelity. The MDM family members are best characterized for their negative regulation of the major tumour suppressor p53 to modulate stress responses. Their impact on other cellular regulators is emerging. Inappropriately elevated protein levels of the MDM family are highly associated with an increased risk of cancer incidence. Exploration of the MDM family members as cancer therapeutic targets is relevant for designing tailored anti-cancer treatments, but successful approaches must strategically consider the impact on both the target cancer and adjacent healthy cells and tissues. This review focuses on recent findings pertaining to the role of the MDM family in normal and malignant breast cells.

Registration Now Open for ACCM2017

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The Australian Cell Cycle Community

It is our pleasure to announce that Registration for #ACCM2017 is now officially open [Link], and is proudly co-sponsored by the Garvan Institute.
The conference will be held from Monday 27-29th of March, 2017 at the Powerhouse Museum in Sydney Australia.
We are also very excited to announce that for the 2017 meeting will bring together the fields of Cell Cycle, DNA damage and Telomeres into one exciting 2-day event. In celebration we have an outstanding line up of International and National Speakers, including:
  • Julia P. Cooper (Telomere Biology Center for Cancer Research Bethesda USA),
  • Daniel Durocher (DNA Damage The Lunenfeld-Tanenbaum Research Institute Toronto Ontario Canada),
  • Marcos Malumbres (CNIO Spain)
  • Antoine van Oijen (Single-molecule biophysics, DNA replication, School of Chemistry, University of Wollongong NSW Australia).
  • +’ lots more
As always the meeting will provide an excellent opportunity to meet, discuss and foster collaborations with leading researchers…

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8th Garvan Signalling Symposium – Registration Now Open !!!

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GarvanSignalling20168th Garvan Signalling Symposium

 Date: Monday 31st of October and Tuesday 1st of November 2016
Venue: The Garvan Institute of Medical Research, Sydney
Registration – Abstract submission to 15th of September 2016
 The Garvan International Signalling Symposium is a premier meeting focused on the mechanisms of signal transduction. It began as a small meeting organised by Prof. Roger Daly around the visit of Prof. Axel Ullrich to the Garvan Institute in 2001. Since then, ‘Signalling Meetings’ have been held every 2-3 years and the meeting has grown into one of the Garvan Institute’s premiere scientific events. This boutique symposium highlights cutting-edge developments from the Asia-Pacific region and the rest of the world.
The Garvan International Signalling Symposium is a premier meeting focused on the mechanisms of signal transduction. It began as a small meeting organised by Prof. Roger Daly around the visit of Prof. Axel Ullrich to the Garvan Institute in 2001. Since then, ‘Signalling Meetings’ have been held every 2-3 years and the meeting has grown into one of the Garvan Institute’s premiere scientific events. This boutique symposium highlights cutting-edge developments from the Asia-Pacific region and the rest of the world.

We welcome scientists at all levels, including students, post-docs, research staff and senior lab heads. The intimate nature of the meeting and enjoyable social functions promotes a collegial atmosphere and excellent networking opportunities. A poster session will be held on the Monday afternoon with generous prizes. Slots have been reserved for short (15 minutes) talks to be selected from submitted abstracts.

The meeting is held at the Garvan Institute in the glamorous Darlinghurst region of Sydney, close to the city, Oxford Street, King’s Cross and the harbour.

This years exciting program features state-of-the-art technologies to investigate a wide range of diseases including cancer, immunology, neuroscience and metabolic disorders.  Special sessions focus on in vivo/intravital signalling, proteomics, control of gene regulation and the structural basis of signalling.

Click Here for more information and to register

 

Speakers

Keynote Speakers

Klaus M Hahn

Klaus HahnThe University of North Carolina at Chapel Hill, USA

Dr. Hahn’s laboratory develops new means to visualize and control protein activity in vivo, and uses them to study the role of signaling dynamics in immune cell decision making. His laboratory has produced broadly applicable approaches to fluorescent biosensors that report conformational changes of endogenous proteins, fluorescent dyes to visualize protein activity in vivo, and protein analogs that can be controlled by light or small molecules. Current biological studies focus on phagocytosis, platelet production and metastasis.

Dr. Hahn studied at the University of Pennsylvania and the University of Virginia, where he received his Ph.D in Organic Chemistry. He was a postdoc at the Center for Fluorescence Research at Carnegie Mellon University, became an Associate Professor of Cell Biology at the Scripps Research Institute, and then moved to UNC-Chapel Hill, where he is the Thurman Distinguished Professor of Pharmacology and Director of the UNC-Olympus Imaging Center. Dr. Hahn is a recipient of an NIH Transformative Grant, the NIH’s James Shannon Director’s Award, and is a fellow of the AAAS. His lab’s work on biosensors was named one of the “10 Breakthroughs of the Decade” by Nature Reviews Molecular Cell Biology.

http://www.hahnlab.com/

 

 

Owen J Sansom

Owen J SansomThe Beatson Institute, Scotland

Owen Sansom is interim director of the Cancer Research UK Beatson Institute, Glasgow. Owen gained his PhD in 2001 working on in vivo models of apoptosis in cancer. Since then, he has been instrumental in determining the molecular hallmarks of colorectal cancer (CRC), including showing the roles of the tumour suppressor protein APC and the WNT signalling pathway and the involvement of intestinal stem cells in tumourigenesis. In 2005, Owen established his own laboratory at the Cancer Research UK Beatson Institute, where he became Deputy Director in 2010. The Sansom laboratory uses in vivo models and 3D in vitro models to recapitulate CRC and pancreatic cancer to investigate the molecular mechanisms underpinning tumourigenesis and to identify novel drug targets. In 2007 Owen won the BACR/AstraZeneca Young Scientist Frank Rose Award and in 2012 was elected a Fellow of the Royal Society of Edinburgh and was awarded the Cancer Research UK Future Leaders in Cancer Research prize.

http://www.beatson.gla.ac.uk/invasion-and-metastasis/owen-sansom-colorectal-cancer-and-wnt-signalling.html

 

International Speakers

Eric O'Neill

Eric O’Neill

University of Oxford, UK

Eric O’Neill is a Senior Group Leader and Associate Professor at the CRUK/MRC Oxford Institute for Radiation Oncology. After completing a Ph.D. at the University of Umeå, Sweden he was a post-doc at the University of Oxford. Subsequently, he was awarded a Marie Curie research fellowship and completed a 5-year post-doctoral position investigating oncogenic and tumour suppressor signalling at the CRUK Beatson Institute for Cancer Research in Glasgow. He is a member of the Association for Radiation Research and an examiner for the Royal College of Radiologists. He has also been on the organising committee for several international conferences.

http://www.radiationoncology.ox.ac.uk/research/eric-oneill

 

PR Shepherd

Peter R Shepherd

University of Auckland, New Zealand

Peter Shepherd gained a PhD in Chemistry from Massey University in New Zealand before post doctoral fellowships at Harvard University and  Cambridge University.  Following faculty positions at University College London, he moved back to Auckland University in 2004 where he is currently deputy director at the Maurice Wilkins Centre, a Centre of Research Excellence. His work focusses on understanding how defects in cell signalling pathways contribute to the development of type-2 diabetes and cancer, particularly focussing on the PI 3-kinase and beta-catenin pathways.  His lab also has a strong translational research focus in the form of several ongoing in house drug discovery projects.

https://unidirectory.auckland.ac.nz/profile/peter-shepherd

 
 
 
 

Tilman Brummer

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University of Freiburg, Germany
 

Dr. Tilman Brummer is currently an independent group leader at the Institute of Molecular Medicine and Cell Research (IMMZ) at the Albert-Ludwigs University (ALU) in Freiburg, Germany. He finished his studies in Biology with a diploma at the ALU followed by a PhD thesis on B lymphocyte signalling with Prof. Michael Reth at the Max-Planck-Institute for Immunobiology and Epigenetics. In 2003, he joined the laboratory of Prof. Roger J. Daly at the Garvan Institute of Medical Research in Sydney as a postdoctoral fellow. In 2008, he returned to the newly established Centre of Biological Systems Analysis (ZBSA) at the ALU to establish his independent laboratory funded by the Emmy-Noether program of the German Research Foundation (DFG) before moving to the IMMZ in 2012. He is a principal investigator within the Collaborative Research Centre 850 “Control of Cell Motility in Morphogenesis, Cancer Invasion and Metastasis”, the “Spemann Graduate School of Biology and Medicine” and the “Centre for Biological Signalling Studies” BIOSS. Recently, he has been awarded a prestigious Heisenberg fellowship of the DFG.

The Brummer laboratory is interested in the organisation of intracellular signalling pathways and how their intricate control becomes disturbed in human cancer. The laboratory is particularly interested in understanding the regulation of the BRAF and GAB2 oncoproteins and how they contribute to metastasis and drug resistance in solid tumours and leukaemia.

 

 

Jen Morton

Jennifer Morton

The Beatson Institute, Scotland
 

Jen Morton is a joint leader of the pancreatic cancer research team at the Cancer Research UK Beatson Institute.  Her research focuses mainly on: (a) Investigating the importance of mutations found in human pancreatic tumours using mouse models, (b) Profiling different genetic subsets of pancreatic cancer to better understand the disease and identify specific targets for therapy, and (c) performing preclinical trials of targeted therapies in clinically and genetically relevant pancreatic cancer mouse models.

 

Pat Caswell

Pat Caswell

Wellcome Trust Centre for Cell-Matrix Research, UK

Patrick is based within the Wellcome Trust Centre for Cell Matrix Research at the University of Manchester. Patrick studied Biochemistry at the University of Nottingham, before undertaking a PhD at the University of Leicester and a postdoc in Jim Norman’s lab at the Beatson Institute for Cancer Research. Patrick set up his lab in 2010, focussing on how cell-matrix interactions through integrins generate signals that control key cellular processes such as cell migration, differentiation and survival. The lab is specifically interested in vesicular trafficking, and has recently shown that endocytic trafficking of integrins and co-cargo receptors controls the spatial activation of RhoGTPases to modulate the actin cytoskeleton in invasive cancer cells.

http://www.wellcome-matrix.org/research_groups/pat-caswell.html

 

Vinay Tergaonkar

Vinay Tergaonker

Institute of Molecular and Cell Biology, Singapore
 

Vinay Tergaonkar obtained his Ph.D. (2001), from National Center for Biological Sciences, Bangalore. During his graduate studies he was awarded an international cancer society (UICC) fellowship for collaborative research at Tufts University, Boston, USA. He has been a fellow (2001-2004) and a special fellow (2004-present) of the Leukemia and Lymphoma Society of America and conducted his postdoctoral studies at the Salk Institute for Biological Studies, La Jolla, California. He joined the Institute of Molecular and Cell Biology (IMCB) in late 2005 as Principal Investigator and became a Senior Principal Investigator in 2010 and Research Director in 2015. He is also a Professor at School of Medicine at National University of Singapore. He has been invited to speak at various international venues and meetings such as the Barossa and Hunter valley meetings in Australia, Genes and Cancer meeting in UK, The Argentine Pharmacological society meeting in Buenos Aires, Aichi and Japanese Cancer Society meetings in Japan and the Keystone Symposia. He serves on 
Editorial Boards of 1) Molecular and Cellular Biology (American Society for Molecular Biology) 2) Biochemical Journal (Portland Press) 
3) Critical Reviews in Oncology/Hematology (Elsevier Press), 4) BMC Research Notes (Biomed Central) and 5) Telomeres and Telomerase. He has received international recognition for his work including the British council development award (2014) and the 2015 Premiers’ fellowship from Government of South Australia.

 

Daniel Schramek

Daniel Schramek

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Canada

Daniel Schramek is a Principal Investigator at the Lunenfeld-Tanenbaum Research Institute, and Assistant Professor in the Department of Molecular Genetics, Faculty of Medicine, University of Toronto. He obtained his BSc and MSc in Molecular biology from the University of Vienna and undertook his master thesis under the supervision of Prof. Roger Daly at the Garvan Institute in Sydney. He undertook his PhD work under the supervision of Prof. Josef Penninger at IMBA in Vienna, followed by postdoctoral studies with Prof. Elaine Fuchs at the Rockefeller University in New York. In 2015, Dr. Schramek was recruited to the Lunenfeld-Tanenbaum Research Institute, where he holds an endowed ‘Kierans & Janigan’ Cancer Research Chair as well as a tier 2 Canadian Research Chair in Functional Cancer Genomics. Dr. Schramek was awarded a prestigious HFSP Career Development Award, the Early Researcher Award from the Ontario Ministry of Research & Innovation as well as a CIHR Foundation grant.

His lab focuses on functional cancer genomics and has generated various in vivo CRISPR-gene editing methodologies to screen for novel tumor suppressors, cancer vulnerabilities as well as therapy resistance genes in various mouse models of human cancers. Through this program, Dr. Schramek specifically aims to identify molecular and cellular mechanisms that regulate epithelial tissue growth in adult homeostasis, cancer and cancer-associated inflammation.

http://www.lunenfeld.ca/researchers/schramek

http://schramek.lunenfeld.ca

 

 

BioEssays Review on Mitotic Phosphatase Specificity now Online

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icl31035-toc-0001

Great News, our review on how phosphatase specificity is controlled during mitosis has been re-published in BioEssays and is now Online!

This review was originally published in Inside the Cell, which unfortunately has shut down.

But the good news is that it is still Open Access, so that means its free for everyone to read! And is now also indexed in PubMed

During mitotic exit, phosphatases reverse thousands of phosphorylation events in a specific temporal order to ensure that cell division occurs correctly. This review explores how the physicochemical properties of the phosphosite and surrounding amino acids affect interactions with phosphatase/s and help determine the dephosphorylation of individual phosphorylation sites during mitotic exit.

The Full-text download for the Article can be found here [Link]

Citation: Rogers, S. et al. (2016) Mechanisms regulating phosphatase specificity and the removal of individual phosphorylation sites during mitotic exit. BioEssays, 38, S24–S32.

 

Save the Date: ACCM2017 – March 27-29th – “Cell Cycle, DNA Damage Response & Telomeres”

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The Australian Cell Cycle Community

2017 Flyer v2-01

The 16th Australian Cell Cycle Meeting: “Cell Cycle, DNA Damage Response & Telomeres” will be held from Monday the 27th to Wednesday the 29th of March, 2017 at the Powerhouse Museum, in Sydney Australia.

The 2017 meeting will be the largest ever ACCM meeting, bringing together the fields of Cell Cycle, DNA Damage Response, and Telomere biology into one amazing meeting.

We are also very excited to announce 4x Plenary Lectures for #ACCM2017:

  • Julia P. Cooper
    Telomere Biology Center for Cancer Research (NCI) Bethesda, MD, USA
  • Daniel Durocher
    DNA Damage The Lunenfeld-Tanenbaum Research Institute Toronto, Ontario Canada
  • Marcos Malumbres
    Cell Division & Cancer National Cancer Research Centre (CNIO) Madrid, Spain
  • Antoine van Oijen
    Single-molecule biophysics, DNA replication Head School of Chemistry, University of Wollongong NSW, Australia
Registration for the ACCM2017 will open in October 2016, and more details, including a fantastic line up of National speakers will be announced…

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