Tuesday 29th November 2016.
Building 20, Room 5, University of Wollongong.
There will be a one-day workshop on Tuesday 29th November with presentations covering the applications of mathematical modelling in the areas of mathematical biology and medicine (interpreted in a broad sense).
The keynote speakers are Professor John Murray (University of New South Wales and Cancer Research Division, NSW Cancer Council) and Dr Kara Perrow (Illawarra Health and Medical Research Institute, UOW).
Supporting presentations will be given by satff/students from UOW, the Australian National University, the University of Notre Dame and the University of Sydney.
Presentations will be aimed at a `general audience'. The emphasis is placed on the problem being investigated and the insights that mathematical modelling provides. Speakers are encouraged to avoid gory mathematical details!
There is no registration fee to attend the workshop. On the other hand, we are not providing you with lunch, a pad of paper, free pens or a workshop bag. However, we will provide afternoon tea. In order to know numbers for catering you are highly encouraged to register!
To register please click on this link.
Program subject to change without warning!
|Session One. Chair: Dr Peter Kim|
|10.00||Dr Kara Perrow|
|Using nanocarriers to overcome drug delivery barriers in cancer therapy|
|Changing the Treatment Paradigm: Ex vivo assessment of gemcitabine eluting fibres for the treatment of pancreatic cancer|
|Controlled release from non-axisymmetric disk|
|11.20||Dr Danya Rose|
|A more realistic agent based model for the Grandmother Hypothesis|
|Mathematical model for checkpoint blockade treatments in cancer immunotherapy|
|Modelling of the lymphatic vascular system|
|12.00||Lunch (not provided).|
|Session Two. Chair: Dr Edward Waters|
|13.30||Professor John Murray|
|Using operations research methods to determine features within founder HIV envelope sequences that differentiate them from chronic virus|
|Can maths help virus's treat cancer? Data driven model creation to optimise therapies.|
|The Diffusion of an Oncolytic Virus within a Solid Tumour|
|Can cellular crowding limit the effectiveness of cancer vaccines? A mathematical model|
|Statistical Methods for quantitative whole body 4D PET Analysis|
|Incorporating cell forces into a multiphase model for collagen gel mechanics|
|Potential impact of a maternal vaccine for RSV: a mathematical modelling study|
|15.30||Afternoon tea (provided)|
|Session Three. Chair: Professor John Murray|
|16.00||Dr Edward Waters|
|Partial immunity to influenza: A simple model with complex dynamics and implications for vaccination|
|Eradication of tobacco smoking: just a pipe dream?|
|A general reaction-diffusion model for acid-mediated tumour growth|
|17.00||Dr Michael Watson|
|Cell Migration and Capillary Plexus Formation: Hybrid Modelling Approaches in Healing, Development and Disease|
|17.20||End of transmission|
Although this workshop is primarily running on the smell of an oily rag, it would not have been possible without financial support from the NSW branch of ANZIAM and the Institute for Mathematics & its Applications.
|Associate Professor M.I. Nelson||School of Mathematics and Applied Statistics, University of Wollongong|
|Dr S. Oktaria||School of Physics, University of Wollongong|
|Associate Professor A. Worthy||School of Mathematics and Applied Statistics, University of Wollongong|
Professor John Murray School of Mathematics and Statistics, UNSW & Cancer Research Division, NSW Cancer Council
Title: Using operations research methods to determine features within founder HIV envelope sequences that differentiate them from chronic virus
Currently there is no vaccine available for HIV despite a number of trials of potential candidates. Determining what is special about the transmitted/founder virus that can be targeted by the immune response is a difficult task. Generally the exposed envelope glycoproteins are the viral component most attacked by antibodies but for this very reason they exhibit high mutation rates. A number of investigators have compared envelope sequences between founder and chronic HIV-infected individuals to see what is different and therefore what might present a reasonable target for vaccine-stimulated antibodies. These comparisons generally compare differences at individual positions of the sequences or between known domains. Here we investigate determining the features that differ between founders and chronics, by using operations research methods.
Dr Kara Perrow, Targeted Cancer Therapeutics Laboratory, Illawarra Health and Medical Research Institute
Title: Using nanocarriers to overcome drug delivery barriers in cancer therapy
Dr Kara Perrow (nee Vine) is Group Leader of the Targeted Cancer Therapeutics Research Laboratory and co-founder of Cancer Drug Discovery Group (CDDG) at the Illawarra Health and Medical Research Institute, University of Wollongong, Australia. She received her PhD from the University of Wollongong in 2007 and has trained internationally in cancer biology and metastasis in research centres such as the Finsen Laboratory, Copenhagen Biocenter, Denmark. Her expertise lies in the field of anticancer drug design and targeted drug delivery and she leads many cross-collaborative and multidisciplinary projects including: development of ligand-directed liposomes for the treatment metastatic breast cancer; implantable drug-eluting polymeric devices for the treatment of pancreatic cancer; development of novel microtubule-targeting drugs and combination anticancer therapies for overcoming multi-drug resistance.
Dr Perrow has authored >25 highly cited publications in leading international journals and holds 3 patents. In the last 5 years Dr Perrow's research has been supported by national and international funding agencies including the National Breast Cancer Foundation, The Motor Neurone Disease Research Institute of Australia, Cancer Australia, Cure Cancer Foundation, The Australian Academy of Science, and the US Department of Defense.
John Brackenbury, School of Mathematics and Applied Statistics, University of Wollongong.
Title: Eradication of tobacco smoking: just a pipe dream?
Each year millions of lives are lost to and billions of healthcare dollars are spent on the treatment of tobacco-related illnesses. Smoking is one of the leading causes of preventable death worldwide. In light of this, many efforts have been made to curtail the rates of smoking through public policy (taxation, banning of advertising etc.), but what strategies are most effective? Is eradication a possibility? Two dynamical epidemiological models are presented to answer these questions.
Alexandra B. Hogan, The Australian National University, Canberra.
Title: Potential impact of a maternal vaccine for RSV: a mathematical modelling study.
Respiratory syncytial virus (RSV) is a major cause of respiratory illness and the main cause of hospitalisations in young children. While there is currently no licensed vaccine for RSV, a vaccine candidate for pregnant women is currently undergoing phase 3 trials. We developed a compartmental differential equation model for RSV transmission, with 75 age classes and cohort ageing. We validated the model using linked RSV hospitalisation data for metropolitan Western Australia. We adapted the model to incorporate a maternal RSV vaccine, and estimated the expected reduction in RSV hospitalisations arising from the vaccine for a range of vaccine coverage, effectiveness and duration scenarios. Introducing a maternal vaccine for RSV was estimated to reduce RSV-related hospitalisations in Western Australia by around 26-40%, assuming coverage similar to existing maternal vaccination programs, and 80% vaccine effectiveness. Children up to six months of age would derive the greatest benefit, in line with the objective of a maternal vaccine to delay the onset of an infant's first RSV infection so as to reduce RSV disease in early life, at the time when symptoms are likely to be more serious.
Bernard Ikhimwin, School of Mathematics and Statistics, University of Sydney.
Title: Modelling of the lymphatic vascular system
The lymphatic vascular system consists of networks of numerous vessels which play a key role in immune surveillance by transporting lymph (a colourless liquid that contains white blood cells that helps to purge undesirable materials and toxins from the body) and protein from the tissue space back to the circulatory system. In contrast to the cardiovascular system which has a central pump, the lymphatic vascular system has no central pump hence the transport of fluid against gravity is driven by extrinsic and intrinsic pumping mechanisms. Disorder of the lymphatic vascular system results in a fluid build-up in the tissues which leads to lymphoedema (swelling of the limbs due to build-up of fluid).
In my talk I will look at lumped parameter models that are used to describe the transport mechanism of the lymphatic vessels.
Adrianne Jenner, School of Mathematics and Statistics, University of Sydney.
Title: Can maths help virus's treat cancer? Data driven model creation to optimise therapies.
Ever considered how effective viruses could be as a cancer killing agent? Currently there are a number of clinical and experimental results which show how promising genetically engineered viruses are at treating cancer. However, there is a still a long way to go before we have a complete cure. So how can maths help? We created a mathematical model of the interaction between an oncolytic adenovirus and tumour cells and matched it to experimental data generated by collaborators in Korea. The model enables the identification and quantification of the processes underlying the dynamics of viral therapy and its effect on breast and cervical cancers. We explored the parameter space of the model to determine the regions of applicability of the system and determine any specific heterogeneity in the behavior of the virus on the differing tumour types. The optimised model is being used to further understand the complex dynamics of the virus-tumour interaction and investigate the optimal application of these therapies.
Adarsh Kumbhari, School of Mathematics and Statistics, University of Sydney.
Title: Can cellular crowding limit the effectiveness of cancer vaccines? A mathematical model
Anti-cancer T cell vaccines are a promising avenue in cancer immunotherapy that activate anti- tumour cytotoxic T lymphocytes (CTLs) aka "killer T cells", but despite showing promise, positive clinical outcomes have yet to be realised. By using an ODE and agent-based framework to model tumour-CTL and T cell vaccine kinetics, we explore if the inefficacy of the CTL response is partly driven by ``crowding out'' dynamics, specifically when low avidity (i.e., weakly tumour-killing) CTLs prevent high avidity CTLs from binding to cancer cell surfaces (and subsequently killing them) via competition for binding spots on target cells.
Mandy Moore, School of Mathematics and Applied Statistics, University of Wollongong.
Title: Statistical Methods for quantitative whole body 4D PET Analysis
The four-dimensional (4D) deconvolution method with spatial and temporal regularisation used in the restoration of positron emission tomography (PET) images involves solving a spectral analysis regression problem for the temporal component of the regularisation. The solution of the fitted regression curve for the activity density of radionuclide present over time (TAC) has previously been validated for the brain region of interest (RoI). Quantification of activity density is important for monitoring physiological function and needs to be accurate for all regions of the body. Assessment of non-negative least squares (NNLS) and three other methods for finding the regression coefficients for the spectral analysis problem was conducted via a Monte-Carlo experiment. Analyses of seven RoI were carried out using NNLS as it was deemed the most reliable method following this simulation-based analysis. However, the covariates of the regression problem are highly correlated and as such lead to unstable estimates across the different RoIs for the NNLS method. The results of the RoI analysis are therefore inconclusive and more research is required to accurately assess the relationship between different RoIs and their associated TACs. This talk will present an overview of the methods utilised and the results of the investigation of the validation of the restoration methods for RoIs within the body - fat, kidney, lung, liver, muscle and myocardium - and assessment of the similarities between the method results for these different RoIs.
Carl Ormerod, School of Mathematics and Applied Statistics, University of Wollongong.
Title: Controlled release from non-axisymmetric disk
Almost all modelling in Spherical and Cylindrical diffusion assumes the geometry is axi-symmetric. An angular dependent mixed boundary value problem is solved analytically for comparison with and calibration of numerical FTCS and MoL models. The pharma-quantities, surface flux and mass transfer, are derived. Possible narrow escape problem application to polymeric micro-devices and diatoms are investigated.
Pantea Pooladvand, School of Mathematics and Statistics, University of Sydney.
Title: The Diffusion of an Oncolytic Virus within a Solid Tumour
One of the biggest barriers in treating solid tumours is the inability of the therapeutic vectors to propagate throughout the tumour mass due to the high density of the tumour and tumour stroma. In this project, we explore this problem by introducing a system of reaction-diffusion equations, including tumour cells and anti-tumour viruses. We find that this system yields interesting oscillatory dynamics induced by diffusion. We also investigate an extension of our initial system by including inhomogeneous diffusion and two new populations to better model the treatment with anti-tumour viruses.
James Reoch, School of Mathematics and Statistics, University of Sydney.
Title: Incorporating cell forces into a multiphase model for collagen gel mechanics
Cells are often grown within collagen gels in vitro for applications in tissue engineering. The behaviour of cells is regulated by their mechanical environment; however the forces exerted by cells in turn affect the mechanical behaviour of the gel. Therefore we aim to gain more insight into the interactions between the cells and the gel using mathematical modelling. In this talk, I will detail how we have incorporated cells and their traction forces into our multiphase model for the gel, alongside chemical effects like osmosis. I will discuss how these forces affect gel swelling and contraction, and how they impact upon the predicted equilibrium outcomes for the gel.
Marianito Rodrigo School of Mathematics and Applied Statistics, University of Wollongong.
Title: A general reaction-diffusion model for acid-mediated tumour growth
I will revisit the modelling of tumour invasion based on the acid-mediation hypothesis, i.e. the assumption that tumour progression is facilitated by acidification of the region around the tumour-host interface. The resulting destruction of the normal tissue environment promotes tumour growth. Gatenby and Gawlinski (1996) proposed a simplified reaction-diffusion system to model this hypothesis. Fasano, Herrero and Rodrigo (2009) used a nonstandard symptotic analysis to study the properties of travelling waves that can be supported by the Gatenby-Gawlinksi model. Subsequently, Holder, Rodrigo and Herrero (2014) proposed an extension that incorporated a nonlinear acid production term. Another direction was given by McGillen, Gaffney, Martin and Maini (2014), where terms representing mutual competition between healthy and tumour cells, as well as acid-mediated tumour cell death, were added to the original Gatenby-Gawlinski model. In this talk I will consider a general reaction-diffusion model that includes the aforementioned models as special cases, with the aim of trying to determine under a quite broad framework the possibility of tumour progression that takes into account the acid-mediation hypothesis.
Danya Rose School of Mathematics and Statistics, University of Sydney.
Title: A more realistic agent based model for the Grandmother Hypothesis
The Grandmother Hypothesis is a possible explanation for the evolution of human post-menopausal longevity, a rare trait among mammals and unique to humans among the primates. As grasslands spread and food sources changed, becoming less ccessible to weaned youngsters without adult help and know-how, it became beneficial for older, less fertile females to take on caregiving roles for their grandchildren, allowing younger, more fertile females to have more children sooner. As more robust elders could provide more help, this spurred the evolution of greater longevity without a corresponding increase in age of menopause.
We discuss a probabilistic agent-based model that incorporates two sexes, mating, fertility-longevity tradeoffs, and the possibility of grandmother help, previously developed by Peter Kim, John McQueen, James Coxworth and Kristen Hawkes. The model is extended to include realistic mortality rates for wild chimpanzees and hunter-gatherers based on a Siler model for mortality and for age-dependent fertility in both cases, based on empirical data, with interpolation depending on a parameter representing longevity.
Samantha Wade, Illawarra Health and Medical Research Institute, School of Biological Sciences, University of Wollongong.
Title: Changing the Treatment Paradigm: Ex vivo assessment of gemcitabine eluting fibres for the treatment of pancreatic cancer
Background: Locally advanced pancreatic cancer (PC) has the lowest survival rate of any cancer (3-10 months). The incidence of PC is almost equal to its mortality, with a 5 year survival of less than 5% for all stages. Less than 20% of patients have resectable tumours, for which surgery is the only potential cure.
Aim: We aim to develop and characterise gemcitabine loaded fibres that will deliver a sustained, lethal dose of drug to PC cells, with the view that they can used to fabricate implantable structures to convert non resectable PC to resectable. Methods: Single polymeric fibres formulated from 1-2% alginate with/without encapsulated gemcitabine were spun using the wet-spinning method. HPLC was used to determine drug encapsulation and drug release profile. In vitro efficacy was assessed using PC cell line MIA-PaCa-2 grown as a 2D monolayer, and MCF-7 cells grown as 3D tumour spheroids (TS). Drug uptake was assessed using doxorubicin loaded 1% alginate fibres and MCF-7 TS. Results: Drug release experiments found that ~85% of drug is released in the first 10h. Gemcitabine loaded fibres showed 57-58% decrease in cell confluency over 72h. Over 17 days, gemcitabine loaded fibres reduced TS diameter by 2-fold, while he empty fibres displayed no toxicity. Uptake studies showed continuous doxorubicin uptake from the fibres over 5h, while equivalent free doxorubicin was rapidly cleared. Conclusions: We have shown that the 1-2% alginate polymeric fibres loaded with gemcitabine displayed a cytotoxic effect on a PC cell line and TS, while the empty fibres did not. The uptake experiment confirmed that there a sustained release system is preferable over bolus systemic dosing. These promising results demonstrate scope for further preclinical evaluation of implantable 3D drug delivery structures manufactured from these fibres for the localised treatment of non-resectable PC.
Edward Waters, University of Notre Dame.
Title: Partial immunity to influenza: A simple model with complex dynamics and implications for vaccination
Initial challenge by an infectious disease (through vaccination or natural infection) can induce an immune response that provides only partial protection against future challenges by genetically similar, though not identical, pathogens. Manifestations of partial immunity include reduced risk of subsequent infections, but also reduced severity and duration of symptoms should subsequent infections occur. Partial immunity is particularly important for Influenza B. Two distinct lineages of Influenza B exist, and prior exposure to one confers only limited protection against infection with the other. In this study, a model is developed where initial infection provides partial protection against future infections with related pathogens. Two basic reproductive numbers are defined, relating to initial infections (R0,1), and subsequent infections with different lineages (R0,2). We demonstrate that disease can only become endemic when R0,1>1, but that periodic outbreaks occur where R0,1<1, which are reminiscent of the trends seen in Influenza B surveillance data. Whilst these parameters produce realistic trends, the effect of vaccination strategies targeting the discordant lineage responsible for secondary infections is, unfortunately, shown to be minimal. The implications of these for the use of vaccines containing more than one Influenza B lineage require further exploration.
Michael Watson, School of Mathematics and Statistics, University of Sydney.
Title: Cell Migration and Capillary Plexus Formation: Hybrid Modelling Approaches in Healing, Development and Disease
Cell migration is a fundamental biological phenomenon that is critical to the development, maintenance and repair of tissues in multi-cellular organisms. A wide variety of micro-environmental factors are known to stimulate the movement of cells, and this presentation will discuss the use of hybrid modelling to study such responses. Within the contexts of wound healing and retinal development, two approaches are considered: the first couples a model of angiogenic neo-vessel growth to a complex representation of blood perfusion, while the second explores cell-cell interactions and the associated consequences for collective cell movement. These dynamic models will be shown to reveal a number of novel insights into the underlying cell behaviour (and should also provide some context for my recent move into the field of atherosclerosis).
Collin Zheng, School of Mathematics and Statistics, University of Sydney.
Title: Mathematical model for checkpoint blockade treatments in cancer immunotherapy
Our potent warrior T-cells have checkpoint proteins, such as PD-1 and CTLA-4, that keep our immune system from attacking ourselves. Unfortunately, cancer cells take advantage of these checkpoints to avoid being attacked by the immune system, thereby evading some of the best anti-tumor weapons in our immune arsenal. As a result, the development of antibody drugs targeting these checkpoints is becoming an increasingly important part of some anti-cancer treatments. Despite promising results, an unexplained phenomenon has been the unexpected delay?roughly three to six months?before the drugs appear to take tangible effect. Such a delay may reflect the notion that inhibiting checkpoints plays only a partial role in unleashing a T-cell response. Two other factors upon which T-cell activation is dependent is antigen simulation via the T-cell receptor (TCR) and co-stimulation via the ligation of the T-cell?s CD28 molecule by molecules on the cancer?s surface, such as B7. We believe that understanding the relationship between the relative levels of checkpoint inhibition, TCR stimulation and CD28 co-stimulation is important to explaining the delay in the efficacy of current checkpoint inhibition drug treatments. We integrate these factors together in a differential equation model with the aim of shedding insight on these novel treatments.