Mosquitoes spread diseases that shorten and worsen the lives of many people, chiefly children in poor countries, around the world. Since Ronald Ross' discovery at the end of the nineteenth century that mosquitoes transmit malaria, field entomologists have collected a great deal of information about mosquito ecology. Despite this tremendous effort, there still remain significant gaps in our knowledge of mosquito ecology, in part, reflecting the significant variation in mosquito ecology across species and geographies. The main aim of this thesis is an attempt to synthesise the substantial information that field entomologists have collected on mosquito lifespan. In Chapters 2 and 3, I conduct meta-analyses of the two predominant approaches used to estimate mosquito lifespan: mark-release-recapture experiments and female mosquito dissection-based studies, respectively. These analyses produce estimates of mosquito lifespan by species and genus, and more broadly, allow for an appraisal of these two experimental approaches. In Chapter 4, I describe a recently developed approach, known as near-infrared spectroscopy, which enables estimation of the age of individual mosquitoes, and then perform an in silico analysis to explore the use of this technology for estimating the average lifespan of wild populations of mosquitoes. The emergence of mosquito resistance to the main insecticides used in vector control, along with the concerning recent discovery that the malaria parasites in Asia are becoming resistant to arteminisin - an important drug used to treat malaria - highlight the need for novel approaches to control disease transmission. Some recently-proposed approaches involve genetic modification of the mosquito vectors, for example, to render them incapable of acting as hosts for disease or to reduce their fecundity. In Chapter 5, I model the impact of a release of mosquitoes carrying a genetic construct known as a homing endonuclease, which has been constructed to bias the sex of mosquito offspring towards males, in computational environments that capture some facets of the real life landscapes where mosquito borne disease is rife. About a century ago, the famous Italian Malariologist Giovanni Grassi declared that malaria was a "giant with clay feet"; reflecting the optimism, in some academic circles at the time, that eradication of this terrible disease would soon occur. Unfortunately, a century of often unsuccessful attempts to control and eradicate malaria, and other mosquito borne diseases, would follow Grassi's statement, meaning that this fight is likely to continue throughout the twenty-first century. We now know much more about mosquitoes and mosquito borne disease than we did a generation ago, but there is still crucial information that we do not. In this thesis, I argue that in order to make significant inroads to disease eradication, further research on mosquito ecology is crucial. Only when we better understand our unwitting mosquito foe, can we design and implement effective disease control measures that are so desperately needed in those most desperate parts of the world.

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The paucity of well validated preclinical models is frequently cited as a contributing factor to the high attrition rates seen in clinical oncological trials. There remains a critical need to develop models which are accurately able to recapitulate the features of human disease. The aims of this study were to use genetically engineered mouse models (GEMMs) to explore the efficacy of novel treatment strategies in HER2 positive breast cancer and to further develop the model to facilitate the study of mechanisms underpinning drug resistance. Using the BLG--HER2KI-PTEN+/- model, we demonstrated that Src plays an important role in the early stages of tumour development. Chemopreventative treatment with dasatinib delayed tumour inititation (p= 0.046, Wilcoxon signed rank test) and prolonged overall survival (OS) (p=0.06, Wilcoxon signed rank test). Dasatinib treatment also induced squamous metaplasia in 66% of drug treated tumours. We used 2 cell lines derived from this model to further explore dasatinib’s mechanism of action and demonstrated reduced proliferation, migration and invasion following in vitro treatment. Due to the prolonged tumour latency and the low metastatic rate seen in this model, further studies were undertaken with the MMTV-NIC model. This model also allowed us to study the impact of PTEN loss on therapeutic response. We validated this model by treating a cohort of MMTV-NIC PTEN+/- mice with paclitaxel and demonstrated prolonged OS (p=0.035, Gehan Breslow Wilcoxon test). AZD8931 is an equipotent signalling inhibitor of HER2, HER3 and EGFR. We observed heterogeneity in tumour response but overall AZD8931 treatment prolonged OS in both MMTV-NIC PTEN FL/+ and MMTV-NIC PTEN+/- models. PTEN loss was associated with reduced sensitivity to AZD8931 and failure to suppress Src activity, suggesting these may be suitable predictive biomarkers of AZD8931 response. To facilitate further studies exploring resistance, we transplanted MMTV-NIC PTEN+/- fragments into syngeneic mice and generated 3 tumours with acquired resistance to AZD8931. These tumours displayed differing resistance strategies; 1 tumour continued to express HER2 whilst the remaining 2 underwent EMT and lost HER2 expression reflecting to a very limited degree some of the heterogeneity of resistance strategies seen in human disease. To further explore resistance to HER2 targeting tyrosine kinase inhibitors, we generated a panel of human cell lines with acquired resistance to AZD8931 and lapatinib. Western blotting demonstrated loss of HER2, HER3 and PTEN in all resistant lines. Acquisition of resistance was associated with a marked change in phenotype and western blotting confirmed all lines had undergone EMT. We used a combination of RPPA and mass spectrometry to further characterise the AZD8931 resistant lines and identified multiple potential novel proteins involved in the resistant phenotype, including several implicated in EMT. In conclusion, when coupled with appropriate in vitro techniques, the MMTV-NIC model is a valuable tool for selection of emerging drugs to carry forward into clinical trials of HER2 positive breast cancer.

La investigación es relevante ya que la gran rapidez en la producción y el consumo de productos OVM, hace que sea necesaria la realización de un estudio adecuado sobre la inadecuada regulación de estos productos en relación al derecho a la información y a la salud del consumidor. Así entonces, la investigación busca analizar sobre todo las implicancias de los OVM en los derechos del consumidor a la información y a la salud, teniendo en cuenta que, los OVM que más se comercializan, comprenden el grupo de alimentos más utilizados por los consumidores como el maíz, la soja, el trigo y el arroz, entre otro más. De modo que, la adopción de garantías de tutela para la gran cantidad de consumidores del mercado peruano es una situación de urgente y necesaria atención. Esta característica de estos productos, es decir su carácter de constituir productos de comercio masivo, hace necesario desarrollar un trabajo mediante el cual se pueda determinar que existen deficiencias en la protección de los derechos a la información y a la salud de los consumidores respecto a los OVM. / Tesis

With the introduction of antibiotics in animal feed becoming less popular, the agricultural industry has begun a shift towards the use of probiotics in animal feed. Since there is no current method to evaluate the risks of using genetically modified probiotics in animal feed. The goal of this project was to create a genetically modified model organism for risk assessment. The genetic marker for that was chosen was GFP that was to be expressed on the surface of the cell. The fluorescent properties allow for visualisation of the genetically modified bacteria and the surface expression would allow for the easy capture and recovery of the bacteria for culturing and cell counts. Genome wide screens were performed using the CW PRED algorithm to locate proteins with LPXTG motif for cell wall anchoring. 16 hypothetical proteins were detected and 6 were selected as candidates for possible surface display of GFP. Of these candidates, the novel L. casei protein LSEI_2320 was found to be expressed at the mRNA during early growth by RT PCR and at then protein level during stationary phase with western blot. This LPXTG protein was found at the surface of L. casei ATCC334 during stationary phase and late stationary phase with immunofluorescence microscopy. A genetically modified L. casei ATCC334 was constructed using the surface protein LSEI_2320 locus as a region for recombination with the pRV300 suicide plasmid. Genetic modification of the locus by the insertion of a GFP reporter region just before the predicted signal peptide site resulted in the abrogation of the expression of LSEI_2320 from the cell surface at the late stationary phase. It appears that this particular gene is not necessary to cell survival even though it is abundantly expressed on the cell surface and can be used as a location for genetic modification in L. casei ATCC334.

Thesis is concentrated on two biotechnologies: biofuels and genetically modified crops. Defines technical and economical characteristics, lists international agreements and czech and european legislation regarding both biotechnologies. Introduces opinions and analyses positions of selected political subjects as UNO, WTO, OECD, EU, catholic church and main czech political parties.

This thesis deals with promoting of the interests in the area of genetically modified organisms. The aim is to analyze the activities of interest groups in the area and affect different approach of governments to GMO in the USA and Europe. The work is structured into four parts. The first chapter theoretically defines interest groups and lobbying. The second chapter is devoted to genetically modified organisms and the differences between the EU and the USA in the legislation, the extent of cultivation and the approach of governments. The third chapter deals with Monsanto - the company that dominates the amount of interest groups in this area. The fourth chapter presents a case study of the problem of genetically modified maize in Europe. Just on the case of genetically modified maize can be seen in the European Union activities interest groups, approach of member states and European Union approach.

Trade Facilitation Indicators have become important mechanisms of monitoring the ease of trade. Another issue of rising concern is the pervasive debate on genetically engineered organisms and the development of Genetically Engineered Restrictive Index to evaluate its implications on trade. With regards to these, the objective of the United States Trade Representative is to eliminate implicit trade barriers. Hence, this study examines the impact of TFIs on U.S. agricultural export and its efficiency. From the results, a 1% increase in destination’s Genetically Engineered Restrictive Index leads to a US$ 9,426.82 and US$ 74,268.04 decline in corn and soybean exports while wheat experiences a US$ 26,204.05 increase. The ‘I-State’ paradox was also revealed from the efficiency rankings. This research recommends that GE labelling policies should be synchronized to match the requirements of the destination countries. Furthermore, information on GE foods must be transparent and disseminated to change destinations’ negative perception.

The detrimental consequences associated with industrial models of food production are becoming more difficult to ignore. In response, one dominant approach to mitigating the myriad environmental, social, and ethical harms relating to food has sought to increase the efficiency of agricultural outputs through scientific and technological innovation. Although technology certainly has some role to play in any vision of a sustainable future, technocratic approaches to problem solving are insufficient—and arguably inappropriate—for addressing many of the kinds of complex challenges that we face today. There are recent indications that both agri-food law and policy and innovation policy are being taken more seriously in Canada, which creates an opportunity to reflect more deliberately on their ends and means. This dissertation explores the topic of how laws, policies, and other tools of governance can work to better align technological innovations in the agri-food sector with shared environmental goals and ethical aspirations. Taking a critical legal perspective closely informed by feminist insights and the work of existing, analogous justice movements, I examine several interlinkages between technology, law, the environment, and society to evaluate some of the failings of existing approaches to food systems transformation and to offer a contribution to the conversation about alternative pathways. Given the context-specific nature of food systems and food systems governance, my focus is primarily on Canada, but the universal importance of food in a globalized world renders some comparative and transnational discussion unavoidable. I use case studies and discourse analysis to demonstrate that, when considered through a justice-oriented lens, several of the new and emerging technologies being championed in the agri-food sector may not be as beneficial as their proponents claim. Instead, they may serve to retrench injustice and cement existing, exploitative power structures, making them more difficult to challenge and change later down the line. Thus, if technologies are to serve public instead of private interests in the ways they are incentivized, designed, regulated, and used, we will need to see broad systemic and structural reforms informed by thoughtful shifts in our values and priorities, rather than merely reactive adjustments to our policies and practices. Though this undertaking will be difficult, it is not impossible; this dissertation offers one way to facilitate the process of seeding change for environmental sustainability and technological justice.

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