QUT Architecture Film Studio (Aus)

Research Statement: An urban film produced by Luke Harrison Mitchell Benham, Sharlene Anderson, Tristan Clark. RIVE NOIR explores the film noir tradition, shot on location in a dark urban space between high-rises and the river, sheltered by a highway. With an original score and striking cinematography, Rive Noir radically transforms the abandoned river’s edge through the production of an amplified reality ordinarily unseen in the Northbank. The work produced under my supervision was selected to appear in the Expanded Architecture Research Group’s International Architecture Film Festival and Panel Discussion in Sydney: The University of Sydney and Carriageworks Performance Space, 06 November 2011. QUT School of Design research submission was selected alongside exhibits by AA School of Architecture, London; The Bartlett School of Architecture, London; University of The Arts, London; Arrhaus School of Architecture, Denmark; Dublin as a Cinematic City, Ireland; Design Lab Screen Studio, Australia; and Sona Cinecity, The University of Melbourne. The exhibit included not only the screening of the film but the design project that derived from and extended the aesthetics of the urban film. The urban proposal and architectural intervention that followed the film was subsequently published in the Brisbane Times, after the urban proposal won first place in The Future of Brisbane architecture competition, which demonstrates the impact of the research project as a whole. EXPANDED ARCHITECTURE 2011 - 6th November Architecture Film Night + Panel Discussion @ Performance Space CarriageWorks was Sydney's first International Architectural Film Festival. With over 40 architectural films by local and international artists, film makers and architects. It was followed by Panel Discussion of esteemed academics and artists working in the field of architectural film.

Strategies and challenges for systematically mapping biologically significant molecular pathways regulating carcinoma epithelial-mesenchymal transition

Enormous progress has been made towards understanding the role of specific factors in the process of epithelial-mesenchymal transition (EMT); however, the complex underlying pathways and the transient nature of the transition continues to present significant challenges. Targeting tumour cell plasticity underpinning EMT is an attractive strategy to combat metastasis. Global gene expression profiling and high-content analyses are among the strategies employed to identify novel EMT regulators. In this review, we highlight several approaches to systematically interrogate key pathways involved in EMT, with particular emphasis on the features of multiparametric, high-content imaging screening strategies that lend themselves to the systematic discovery of highly significant modulators of tumour cell plasticity.

Targeted therapies in non-small cell lung cancer

The majority of non-small cell lung cancer (NSCLC) patients present with advanced disease and with a 5 year survival rate of <15% for these patients, treatment outcomes are considered extremely disappointing. Standard chemotherapy regimens provide some improvement to ~40% of patients. However, intrinsic and acquired chemoresistance are a significant problem and hinder sustained long term benefits of such treatments. Advances in proteomic and genomic profiling have increased our understanding of the aberrant molecular mechanisms that are driving an individual's tumour. The increased sensitivity of these technologies has enabled molecular profiling at the stage of initial biopsy thus paving the way for a more personalised approach to the treatment of cancer patients. Improvements in diagnostics together with a wave of new targeted small molecule inhibitors and monoclonal antibodies have revolutionised the treatment of cancer. To date there are essentially three targeted agents approved for clinical use in NSCLC. The tyrosine kinase inhibitor (TKI) erlotinib, which targets the epidermal growth factor receptor (EGFR) TK domain, has proven to be an effective treatment strategy in patients who harbour activating mutations in the EGFR TK domain. Bevacizumab a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) can improve survival, response rates, and progression-free survival when used in combination with chemotherapy. Crizotinib, a small-molecule drug, inhibits the tyrosine kinase activity of the echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) fusion protein, resulting in decreased tumour cell growth, migration, and invasiveness in patients with locally advanced or metastatic NSCLC. The clinical relevance of several other targeted agents are under investigation in distinct molecular subsets of patients with key "driver" mutations including: KRAS, HER2, BRAF, MET, PIK3CA, AKT1,MAP2K1, ROS1 and RET. Often several pathways are activated simultaneously and crosstalk between pathways allows tumour cells to escape the inhibition of a single targeted agent. This chapter will explore the clinical development of currently available targeted therapies for NSCLC as well as those in clinical trials and will examine the synergy between cytotoxic therapies.

The role of the Eph and ephrin proteins in prostate cancer

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer related deaths in Australian men. Treatment in the early stages of the disease involves surgery, radiation and/or hormone therapy. However, in late stages of the disease these treatments are no longer effective and only palliative care is available. Therefore, there is a focus on exploration of novel therapies to increase survival and treatment efficacy. Advanced prostate cancer is characterised by bone or other distant metastasis. Spreading of the primary tumour to a secondary location is a complex process requiring an initial loss in cell-cell adhesion followed by increased cell migration and invasion. One gene family that has been known to affect cell-to-cell contact in other model systems are the Eph receptor tyrosine kinases. They are the largest family of receptor tyrosine kinases made up of 14 vertebrate Eph receptors that bind to nine cell membrane bound ephrin ligands. Eph-ephrin interaction is crucial in regulating cell behaviour in developmental processes and it is now thought that the underlying mechanisms involved in development may also be involved in cancer. Aberrant expression has been reported in many human malignancies including prostate cancer. Furthermore, expression has been linked with metastasis and poor prognosis in other tumour models. This study explores the potential role of the Eph receptor family in prostate cancer, in particular the roles of EphA2, EphA3 and ephrin-A5. Gene expression profiles were established for the Eph family in a series of prostate cancer cell lines using quantitative real time RT-PCR. A smaller subset of the most prominently expressed genes was chosen to screen a cohort of clinical samples. Elevated levels of EphA2, EphA3 and their ligands, ephrin-A1 and ephrin-A5 were observed in individual cell lines. Interestingly high EphA3 expression was observed in the androgen responsive cell lines while EphA2 was more prominent in the androgen independent cell lines. However, studies using 5-dihydrotestosterone suggest that EphA3 expression in not regulated by androgen. Cells expressing EphA2 showed a greater ability for migration and invasion while cells expressing EphA3 showed poor migration and invasion. Forced expression of EphA2 in the LNCaP cell line resulted in a more invasive phenotype while forced expression of EphA3 in the PC-3 cell line suggests a possible negative effect for EphA3 on cell migration and invasion. Cell signalling studies show activation of EphA2 decreases activity of proteins thought to be involved in pathways regulating cell movement including Akt, Src and FAK. Changes to the activation status of Rho family members, including RhoA and Rac1, associated with reorganisation of the actin cytoskeleton, an important part of cell migration was also observed. As a result, activation of EphA2 in PC-3 cells resulted in a less invasive phenotype. A novel finding in this study was the discovery of a combination of two EphA2 Mabs able to activate EphA2. Preliminary results show a potential for this antibody combination to reduce prostate cancer invasion in vitro. A unique aspect of Eph-ephrin interaction is the resulting bi-directional signalling that occurs through both the receptor and ligand. In this study a potential role for ephrin-A5 mediated signalling in prostate cancer was observed. LNCaP cells express high levels of EphA3 and its high affinity ligand ephrin-A5. In stripe assays, used to study guidance cues, LNCaP cells show strong attraction/migration to EphA3-Fc stripes but not ephrin-A5-Fc stripes suggesting ephrin-A5 mediated reverse cell signalling is involved. Knockdown of ephrin-A5 using shRNA resulted in a decrease in attraction/migration to EphA3-Fc stripes. Furthermore a reduction in proliferation was also observed in vitro. A subcutaneous xenograft model using ephrin-A5 shRNA cells versus controls showed a decrease in tumour formation. This study demonstrates a difference in EphA2 and EphA3 function in prostate cancer migration/invasion and a potential role for ephrin-A5 in prostate cancer cell adhesion and growth.

Martha and her sisters : women in films about journalism

HBO's Hemingway and Gellhorn (Philip Kaufman, 2012), broadcast in May on US television and starring Nicole Kidman as the pioneering female foreign correspondent, hasn't been well reviewed by the majority of critics. Variety described the biopic (with Clive Owen as Hemingway) as “swollen and heavy-handed”, while the Huffington Post declared it an “expensive misfire … a gigantic missed opportunity, a jaw-droppingly trying waste of time”. Regardless of whether such criticisms are fair—as this essay went to press I had been unable to see the film, so I cannot judge one way or the other—Hemingway and Gellhorn should be viewed as a significant addition to the filmography of journalism, retrieving from history as it does the achievements of one of the most significant of the early female practitioners. Gellhorn was a pioneer in a patriarchal press universe, a foreign and war correspondent at a time when this branch of the profession was seen very much as man's work. She covered the Spanish Civil War and the Second World War, and with just as much viscerality as any man.

Hydrogel microwell arrays allow the assessment of protease-associated enhancement of cancer cell aggregation and survival

Current routine cell culture techniques are only poorly suited to capture the physiological complexity of tumor microenvironments, wherein tumor cell function is affected by intricate three-dimensional (3D), integrin-dependent cell-cell and cell-extracellular matrix (ECM) interactions. 3D cell cultures allow the investigation of cancer-associated proteases like kallikreins as they degrade ECM proteins and alter integrin signaling, promoting malignant cell behaviors. Here, we employed a hydrogel microwell array platform to probe using a high-throughput mode how ovarian cancer cell aggregates of defined size form and survive in response to the expression of kallikreins and treatment with paclitaxel, by performing microscopic, quantitative image, gene and protein analyses dependent on the varying microwell and aggregate sizes. Paclitaxel treatment increased aggregate formation and survival of kallikrein-expressing cancer cells and levels of integrins and integrin-related factors. Cancer cell aggregate formation was improved with increasing aggregate size, thereby reducing cell death and enhancing integrin expression upon paclitaxel treatment. Therefore, hydrogel microwell arrays are a powerful tool to screen the viability of cancer cell aggregates upon modulation of protease expression, integrin engagement and anti-cancer treatment providing a micro-scaled yet high-throughput technique to assess malignant progression and drug-resistance.

Aha! The return of Alan Partridge

Throughout a long and occasionally distinguished career first as a television sports correspondent, then chat show host (dramatically ended by the accidental homicide of a guest live on air), then rebirth as a radio presenter at North Norfolk Digital, Alan Partridge has navigated the stormy waters of the British media landscape, now achieving mainstream success on the big screen with a starring role in Steve Coogan’s Alpha Papa (Declan Lowney, 2013). A man who in his desperation for a television series of his own once sank so low as to pitch a show called Monkey Tennis to the BBC finally finds his inner hero in a film which, while presenting mainly as comedy, also contains a biting critique of trends in the British media with which all journalists and media practitioners in general will be familiar. Alpha Papa is a nostalgic, elegiac riff on the pleasures and values of local radio the way it used to be, exemplified by North Norfolk Digital’s stable of flawed, but endearing jocks – Wally Banter, Bruno Brooks, Dave Clifton (who in one scene recounts the depths to which he sank as an alcoholic, drug addicted wreck—“I woke up in a skip with someone else’s underpants in my mouth. I can laugh about it now …”), and Pat Farrell. 50- something Pat is sacked by the new owners of North Norfolk Digital, who in their efforts to transform the station into a “multiplatform content provider” going by the more Gen Yfriendly name of Shape (“the way you want it to be”), wish to replace him with a younger, brattish model lacking in taste and manners. Out go records by the likes of Glen Campbell and Neil Diamond (“You can keep Jesus Christ”, observes Partridge after playing Diamond’s Sweet Caroline in a demonstration of the crackling radio repartee for which he is by now renowned, “that was the king of the Jews”), in comes Roachford. Pat, grieving his dead wife Molly, finally snaps and turns the glitzy media launch of Shape into a hostage siege. Only Alan Partridge, it seems, can step in and talk Pat out of a looming catastrophe.

From cinema to TV : still the same old stories about journalism

Television drama used to be the poor relation of the full length feature film made for cinema. No self-respecting movie star would be seen dead in the former, and successful TV actors rarely sustained careers of comparable brilliance in the film industry. Those days are gone, if a series such as House of Cards is any indicator of the trends.

Talk2Me : the art of augmenting conversations

This paper describes an interactive installation work set in a large dome space. The installation is an audio and physical re-rendition of an interactive writing work. In the original work, the user interacted via keyboard and screen while online. This rendition of the work retains the online interaction, but also places the interaction within a physical space, where the main 'conversation' takes place by the participant-audience speaking through microphones and listening through headphones. The work now also includes voice and SMS input, using speech-to-text and text-to-speech conversion technologies, and audio and displayed text for output. These additions allow the participant-audience to co-author the work while they participate in audible conversation with keyword-triggering characters (bots). Communication in the space can be person-to-computer via microphone, keyboard, and phone; person-to-person via machine and within the physical space; computer-to- computer; and computer-to-person via audio and projected text.

Exploring community building with an awareness display

In this paper, we present a field trial of a pervasive system called Panorama that is aimed at supporting social awareness in work environments. Panorama is an intelligent situated display in the staff room of an academic department. It artistically represents non-critical user generated content such as images from holidays, conferences and other social gatherings, as well as textual messages on its display. It also captures images and videos from different public spaces of the department and streams them onto the Panorama screen, using appropriate abstraction techniques. We studied the use of Panorama for two weeks and observed how Panorama affected staff members' social awareness and community building. We report that Panorama simulated curiosity and learning, initiated new interactions and provided a mechanism for cherishing old memories.