Dr Nathan Godde’s Report

CASS 2012 Travel Grant Report by Dr Nathan Gödde, Peter MacCallum Cancer Centre.

In June-July 2012 Dr Nathan Gödde attended Breast Cancer research conferences in Spain and Italy:
“I am a third year post-doctoral scientist in the laboratory of Dr Patrick Humbert at the Peter MacCallum Cancer Centre in Melbourne and fortunately gained support from the CASS Foundation to present my work at the Congress for the European Association for Cancer Research (Spain) and the Gordon Mammary Gland Biology Conference and preceding 2 day Gordon Seminar (Italy) in June/July 2012. My research utilises mouse models and three dimensional organoid cultures to study the consequences of polarity loss during breast cancer development. Cell polarity refers to the ability of cells to organise themselves in a functionally appropriate manner. In cancer, cells progressively become disorganised and the underlying molecular pathways that control polarity are disrupted. Our laboratory has begun to demonstrate how disruption to core polarity genes such as Scribble can initiate and contribute to breast tumour progression. Support from the CASS Foundation has allowed me to present my breast cancer research at a critical time for my project and career development.

“In the past three years I have gained experience in using mouse models of mammary gland development and cancer. I have prepared a manuscript showing that deletion of the polarity gene Scribble in the mouse mammary gland results in the formation of pre-malignant lesions, hyperactivation of tumour promoting pathways and accelerated tumour progression. It was an exceptional opportunity to attend international meetings on mammary gland biology and cancer prior to publication of this work.

“The Gordon Mammary Gland Biology meetings are held at the Il Ciocco resort in Barga, Italy and are highly regarded and long standing meetings within the mammary gland research community. This is a beautiful and secluded setting in the hills of rural Tuscany and well suited for a small scientific gathering (see attached photo). The meeting was supported by a number of charity foundations but particular comment was made by the organisers that the largest contribution for support was from an Australian charity, the National Breast Cancer Foundation. In addition, Australian scientists were well represented at the meeting due to travel awards such as that afforded to me by the CASS Foundation.

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“This year the organisers introduced a two day seminar series prior to the conference. This seminar series encouraged junior researchers to present their work and network with future collaborators. It also offered the chance for early career researchers to participate in questions and discussion prior to the larger conference.

“I was encouraged by these early discussions to be much more active during debate amongst world leaders during the following conference. To take the microphone at a high level scientific meeting and speak is a thrilling forward step in most young researchers’ careers and Gordon meetings provide the perfect opportunity to gain these experiences. It also allowed me to meet other early career researchers and have time to solidify those connections and friendships before the conference began. By the end of the meeting I had been offered a number of reagents and potential collaborations involving novel genetic crosses using transgenic mice developed in other laboratories.

“The conference sessions were separated into distinct developmental aspects of mammary gland biology beginning with the cellular origins of breast cancer followed by pre-pubertal development, differentiation, breast cancer, post-pubertal development, pregnancy, lactation and Involution. Each session begun with a short talk by the chair providing background on the topic and highlighting the most recent and relevant research. This was a great learning opportunity and really set the stage for the following research presentations. There was a lot of time reserved for questions and discussion, more than other conferences I have previously attended and it was fantastic to be part of those discussions with key leaders in the field.

“A number of presentations were highly relevant to my work. In fact, a poster and short presentation was made by the laboratory of Dr Senthil Muthuswamy, who performs similar studies on the role of Scribble in the mammary gland. Attending this meeting allowed me the opportunity to compare and defend my work against other related unpublished work in front of our peers. Other presentation highlights for me included those from the laboratory of Andrew Ewald. His laboratory characterises changes in cell polarity and movement using three dimensional organoid cultures coupled with real-time fluorescence microscopy. These presentations consisted of detailed movies of cell movements, highlighting the changes in mammary cell molecular composition as the mammary epithelial cells organise themselves into organoids or dissipate in a way that mimics cancer invasion.   Another highlight for me was seeing the work of Patrick Derksen, who like our laboratory uses mouse models and cell culture to investigate the role of junctional polarity proteins in breast cancer. It was inspirational for me to see how you can complement mouse models of cancer with nifty biochemistry to dissect key mechanisms of disease.

“The Congress for the European Association of Cancer Research in Barcelona differed greatly from my participation at the Gordon meetings. There was over 2,500 attendees and covered a whole range of studies from basic research such as mine, all the way to frontline translational and clinical research. I was able to meet with members of two Spanish laboratories face to face as I had planned, and had time to discuss my work and gain some useful feedback. Whilst not as personal as the Gordon meetings, this meeting exposed me to the work and ideas of leading world cancer researchers. These presentations consisted of many high impact studies which are shaping the future of cancer research. For example, Paolo Pandolfi presented his ceRNA hypothesis (Cell 146, August 5, 2011) which will impact on biology more broadly as a whole. He demonstrates that long non-coding RNA’s and pseudogenes (transcribed from so called junk DNA), can “talk” with coding RNA’s via common microRNA binding motifs which result in competition between limiting pools of microRNA’s. This represents a whole new layer of gene regulation and will impact on biology and medical research more broadly. It also impacts on how I design my research into the future.

“The theme of the meeting was on the personalisation of cancer treatment. Traditionally cancer has been treated with broad spectrum chemotherapies which generally target cell proliferation or DNA damage and repair. With modern advances in basic cancer research, molecularly targeted therapies have been developed which can inhibit specific pathways mutated in cancer. How to develop and match the most suitable targeted therapies to the right patients has proven difficult. Many of the talks at this meeting demonstrated how this can be done by 1) using advanced sequencing and gene profiling technologies to identify the range of genetic lesions in specific cancers 2) to identify secondary resistance pathways to target with the use of combination therapies and 3) to use more innovative clinical trial designs such as small scale trials including only those cancer patients that have specific genetic lesions which match the targeted therapy.

“This was best showcased in the plenary lecture by Jose Baselga “The future of personalised medicine”. There was also an education component to the meeting with educational sessions which covered topics such as sequencing, bioinformatics, biomarkers, clinical trial design, cancer immunotherapy and drug design/development. The “meet the expert” sessions offered us the chance to meet the editor of Nature Journal or discuss how to organise cancer research with management from Cancer Research UK (the world’s biggest cancer charity and predominant funder of cancer research in the UK). These sessions also exposed me to discussions with experts on new emerging technologies relating to molecular diagnostics or systems/network biology. Cancer research encompasses a diverse range of technologies and fields. I found attending this meeting gave me broader understanding of cancer biology and in new approaches to cancer research. In addition, my knowledge from talks such as how to organise cancer research is relevant not just to my specific area of research but more broadly as a scientist within my own cancer research institute, the Peter MacCallum Cancer Centre.

“On my return to Australia I arranged to present highlights from the above meetings to over 50 researchers at the Peter MacCallum Cancer Centre and some additional research groups from St Vincent’s Hospital in East Melbourne and the Walter and Eliza Hall Research Institute in Parkville, Melbourne. The presentation was for an hour and generated some great discussions. I have also been able to make available the abstract books from these meetings and my notes to some researchers with an interest in posters and talks I did not cover in detail in the presentation.

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“As a whole this was a great experience. I was able to make important contacts and defend my work on the international stage. I have agreed with my laboratory head to attend the Gordon Mammary Conference every year as it provides great exposure for our laboratory’s breast cancer work, has great potential to mediate fruitful collaborations and it benefits my work greatly. I would like to thank the CASS Foundation committee for my favourable consideration for travel support to attend these meetings. It was altogether an amazing opportunity at this juncture of my career and I would like to highly recommend future support for other young Australian breast cancer researchers seeking to attend the Gordon Mammary Seminar and Conference in future years.”

Nathan Gödde, PhD
Post-Doctoral Scientist
Cell Cycle and Cancer Genetics Laboratory
Peter MacCallum Cancer Centre
www.petermac.org