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Cell surface mannan oligosaccharides have been implicated in die pathogenesis of C. albicans through roles such as adhesion to host cells and modulation of the immune system (Calderone, 1993, Chaffin, 1998). Understanding the molecular biology of glycosylation is therefore critical to elucidating host-fungus interactions. The CaMNTI gene, responsible for adding the second mannose on 0-linked mannan has previously been shown to be important for adhesion and virulence in C. albicans (Buurman et ai, 1998). In this project, the CaMNT1 gene family was studied as a means to understand more about the roles of oligosaccharide synthesis in Candida-host interactions. The Camntlp enzyme was expressed heterologously in P. pastoris and its cofactor and acceptor specificities were determined. The key residues for the retaining mechanism of CaMntlp catalysis and for cofactor binding were determined by site-directed mutagenesis as Asp350, Glu-318, His-377 and His377. This knowledge may aid in the rational design of antifungals against the MNT1 family of Candida mannosyltransferases. Two further members of the gene fainily; CaMNT3 and CaMNT5 were disrupted using the ura-blaster technique. Deletion of CaMNT3 and to a lesser extent CaMNT5 led to strains unable to form hyphae on solid Spider medium. This phenotype is distinct from that reported for CaMNT1 and suggests a role for these genes upstream or downstream of the Cphlp MAP Itinase cascade that regulates yeast-hypha morphogenesis. The Camnt3 and CamntS nuU mutants were attenuated in virulence in a systemic mouse model of candidosis. The heterozygous mutants were more attenuated in virulence than the nuU mutants indicating that a compensation mechanism may upregulate expression of other MNT genes when both copies of CaMNTS or CaMNT3 are disrupted. This study has shown that glycan synthesis affects morphogenesis in C. albicans and indicates many cell wall proteins require to be glycosylated to perform their function.

The spread of human immunodeficiency virus and other infection through drug injecting and sexual risk behaviour raises important considerations for social policy. The aims of this thesis are broadly two-fold. First, to explore and understand more about the influences on drug injectors' risk behaviour and how these influences might operate inside and outside prison. Second, to consider the impact of policy on drug injectors' lives and subsequent risk behaviour. To examine these issues a qualitative approach was adopted. Four research methods were used: in-depth interviews, a vignette, small group discussions and diary field notes. Drug injectors were contacted in the community and a total of 24 drug injectors with prison experience participated. The empirical component of the research was underpinned by the development of a new theoretical framework towards conceptualising risk behaviour. Inductive and deductive qualitative data analysis categorised perceptions of risk into three broad themes revolving around risky situations, influences on and mechanisms of risk reduction, and responses to risk behaviour. Drug injectors' views and experiences on three policy topics - the role and operation of prison drug and injecting equipment markets, mandatory drug testing, and substitute drug prescribing - were explored. This thesis raises important implications for the ways drug injectors' risk behaviour is understood and how policy responses can be better informed. Ultimately, there is a need for policies to reduce drug-related harm amongst drug injectors, especially when they spend time inside prison. That this is missing from current policy agendas results in people putting themselves and others at risk of infection.