Team:UCL/Modeling

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<p class="major_title">WHAT IS ALZHEIMER'S?</p>
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<p class="major_title">DRY LAB</p>
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<p class="minor_title">Modelling The Treatment And Finding New Parts</p>
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Mathematical modelling provides a powerful tool for scientists of all disciplines, allowing inspection and manipulation of a system in ways which are unachievable in the lab. In the context of biology, we can use mathematical models to study the behaviour of a single cell or an entire ecosystem. In fact, inspecting a mathematical model is very much like a laboratory experiment – the main difference being that in modelling, the environment is artificial. <br><br>
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Click the abstracts below to read more.
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<p class="minor_title">A Form Of Dementia</p>
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Dementia is an age related neurodegenerative condition, characterised by failure of recent memory and intellectual functions (attention, language, visual-spatial orientation, abstract thinking, judgement), and tends to progress steadily <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312395/" target="_blank">(Weintraub et al. 2012)</a>. These changes are due to the mounting dysfunction and death of brain cells, called neurons, which are responsible for the storage and computation of information. Late stages of the disease often see patients bedridden, mute and incontinent. Although some drugs can temporarily improve memory, pharmaceutical research, through enlightening, has been clinically unsuccessful.  At present there are no treatments that can halt, let alone revert, the inexorable progression of dementia. The treatments that do exist are purely symptomatic <a href="http://www.ncbi.nlm.nih.gov/pubmed/20431570" target="_blank">(Citron 2010)</a>.
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Alzheimer’s disease (AD) is the most common of the dementias, afflicting 5-10% of the US population over 45, and 2% of the population in industrialised countries <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091392/" target="_blank">(Mattson 2004)</a>. It is
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predicted that its incidence will rocket up threefold 50 years from now <a href="http://www.alz.org" target="_blank">(http://www.alz.org)</a>.
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It is mainly ‘late-onset’, arising after the age of 60, though rarer early onset types exist. Because there are other forms of dementia and other means of memory impairment, AD can only be verified post-mortem by examining the deceased’s brain.
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Mathematical modelling provides a powerful tool for scientists of all disciplines, allowing inspection and manipulation of a system in ways which are unachievable in the lab. In the context of biology, we can use mathematical models to study the behaviour of a single cell or an entire ecosystem. In fact, inspecting a mathematical model is very much like a laboratory experiment – the main difference being that in modelling, the environment is artificial.  
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In the early stages of AD may suffer lapses in their memory and struggle to find the correct words and expressions. As the patient grows older, the disease worsens and they become increasingly confused, forgetting names, faces, dates, times, etc <a href="http://www.ncbi.nlm.nih.gov/pubmed/23923594" target="_blank">(Sharma 2012)</a>. They tend to experience mood swings and commonly sadness, fear as well as becoming irate as their memory loss increases. This commonly engenders social withdrawal and can make carrying out  everyday tasks much more demanding. As the disease runs near the end of its course and the patients’ lives, they will require help and focused care from those around them - friends, family and health professionals, in order to continue to enjoy their lives to the best of their ability.
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For all the complex calculations and mechanisms behind a model, it is without much worth if it cannot produce useful results. In general, 'useful results' are defined as successful predictions about the effects of modifying some parameter - if we can use a model to determine the effect of each variable upon the outcome, we can better design our system in the real world.  
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The abilities to think, feel and imagine of those affected will diminish; The patients’ sense of self, personality, even their ability to swallow, will all degrade. AD also frequently has a traumatising effect on family members and close friends. As life expectancies increase, this state of life is set to grow much more common <a href="http://www.ncbi.nlm.nih.gov/pubmed/16360788?dopt=Abstract" target="_blank">(Ferri et al. 2005)</a>. It is a truly terrifying condition, and throughout our research we have been amazed by how hard many spirited sufferers, their family and their friends, struggle against the disease and continue to make the best of themselves.
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Since Westminster's iGEM team had not produced a model of their own, and their project has several similarities to ours, we have constructed an additional model, also in C#, and sent this to Westminster's team for them to use. The model simulates bed bugs moving randomly in a cubic room. One of their proposed "blood traps" is integrated into the simulation, which visually demonstrates bed bugs being attracted and then subsequently killed by the device.  
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It may then seem surprising that research efforts into cancer treatments dwarf dementia research <a href="http://www.ncbi.nlm.nih.gov/pubmed/15685097?dopt=Abstract" target="_blank">(Bonin-Guillaume 2005)</a>. Pharmaceutical companies have recently more or less halted their efforts to search for pharmacological solution for AD. This has inspired some scientists to consider novel approaches to combating AD. We see synthetic biology as one of those fields, but new avenues of neuro-genetic research could well bring about genetic modification of the brain for more than just medical reasons.
 
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More information about the condition, including current research, and advice about coping with and caring for AD patients can be found  through the <a href="http://www.alzheimers.org.uk/" target="_blank">Alzheimer’s Society</a>, <a href="http://www.alz.co.uk/" target="_blank">Alzheimer’s Disease International</a>
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<p class="abstract_text">Using bioinformatics we can identify key genes whose dysfunction drives disease states. In so doing, we are should be able to come up with new parts that target these dysfunctional genes to increase the efficacy of synthetic biological constructs. 
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and the <a href="http://www.alz.org/" target="_blank">Alzheimer’s Association</a>.
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Latest revision as of 03:56, 5 October 2013

DRY LAB

Modelling The Treatment And Finding New Parts

Mathematical modelling provides a powerful tool for scientists of all disciplines, allowing inspection and manipulation of a system in ways which are unachievable in the lab. In the context of biology, we can use mathematical models to study the behaviour of a single cell or an entire ecosystem. In fact, inspecting a mathematical model is very much like a laboratory experiment – the main difference being that in modelling, the environment is artificial.

Click the abstracts below to read more.

Model Overview

Mathematical modelling provides a powerful tool for scientists of all disciplines, allowing inspection and manipulation of a system in ways which are unachievable in the lab. In the context of biology, we can use mathematical models to study the behaviour of a single cell or an entire ecosystem. In fact, inspecting a mathematical model is very much like a laboratory experiment – the main difference being that in modelling, the environment is artificial.

Simulation Results

For all the complex calculations and mechanisms behind a model, it is without much worth if it cannot produce useful results. In general, 'useful results' are defined as successful predictions about the effects of modifying some parameter - if we can use a model to determine the effect of each variable upon the outcome, we can better design our system in the real world.

Westminster collaboration

Since Westminster's iGEM team had not produced a model of their own, and their project has several similarities to ours, we have constructed an additional model, also in C#, and sent this to Westminster's team for them to use. The model simulates bed bugs moving randomly in a cubic room. One of their proposed "blood traps" is integrated into the simulation, which visually demonstrates bed bugs being attracted and then subsequently killed by the device.

Bioinformatics

Using bioinformatics we can identify key genes whose dysfunction drives disease states. In so doing, we are should be able to come up with new parts that target these dysfunctional genes to increase the efficacy of synthetic biological constructs.

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