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Macrophages clear infections by engulfing and digesting pathogens within phagolysosomes. Pathogens escape this fate by engaging in a molecular arms race; they useWxxxEmotif- containing “effector” proteins to subvert the host cells they invade and seek refuge within protective vacuoles. Here we define the host component of the molecular arms race as an evolutionarily conserved polar ‘hotspot’ on the PH-domain of ELMO1 (Engulfment and CellMotility1), which is targeted by diverseWxxxE-effectors. Using homology modeling and site- directed mutagenesis, we show that a lysine triad within the ‘patch’ directly binds allWxxxE- effectors tested: SifA (Salmonella), IpgB1 and IpgB2 (Shigella), and Map (enteropathogenicE. coli). Using an integrated SifA•host protein-protein interaction (PPI) network,in-siliconetwork perturbation, and functional studies we show that the major consequences of preventing SifA•ELMO1 interaction are reduced Rac1 activity and microbial invasion. That multiple effectors, all diverse in structure, function, and sequence bind the same hotpot on ELMO1 suggests that theWxxxE-effector(s)•ELMO1 interface is a convergence point of intrusion detection and/or host vulnerability. We conclude that the interface may represent the fault line in co-evolved molecular adaptations between pathogens and the host and its disruption may serve as a therapeutic strategy.GRAPHICAL ABSTRACTIn briefThis work defines the nature of a conserved molecular interface, assembled between diverse WxxxEmotif- containing effector proteins encoded by gut pathogens and the host innate immune sensor, ELMO1, via which pathogens exploit the host’s engulfment machinery.HIGHLIGHTSGut pathogens trick macrophages to enter and form vacuoles of refuge within the host.Diverse pathogens useWxxxEmotif-containing effectors to bind a conserved surface on ELMO1.WxxxE-effector•ELMO1 interaction activates Rac1 and promotes bacterial invasion.Disrupting theWxxxE-effector•ELMO1 interface may serve as a therapeutic strategy.

Employing an expanded meaning of the concept of sense of place within Health Geography, this thesis explores the relationship between sense of place and mental wellbeing of immigrants. The concept of sense of place demonstrates the importance of specific places for socioeconomic and health impacts on individuals and groups in their societies. While research has explored immigrants’ sense of place, few studies have attempted to explore visible minority’s perceptions of place and its influence on wellbeing. Using qualitative and quantitative techniques, this thesis explores the perceptions and experiences of place amongst Ghanaian and Somali immigrants in Hamilton, Ontario, Canada. First, we explore key informants’ revelations on immigrants’ sense of place and mental wellness in Hamilton, Ontario. Findings provide insight into the role of policies that affect determinants of health amongst immigrants. Second, we examine the effects of self-perceived mental wellness, socioeconomic and demographic variables on sense of place amongst Ghanaian and Somali immigrants living in Hamilton, based on an analysis of a survey questionnaire (n=236). Findings highlight a positive relationship between sense of place and mental wellness. Third, using descriptive and multivariate regression methods, we focus on factors that predict African immigrants’ life satisfaction in Canada. We examine sociodemographic, economic and health-related factors that predict life satisfaction amongst African immigrants, specifically Ghanaian and Somali immigrants. We find that immigrant settlement workers and agencies would be better able to meet the needs of immigrants if they are conscious of the factors that would empower immigrants to cope with life stresses. We suggest a reduction of stress by helping individuals and families identify sources of support, providing jobs, affordable housing, language interpretation and training. Lastly, we explore specific places, religious sites and their relationship to health and wellbeing for immigrants. Specifically, we explore churches and mosques where Ghanaian and Somali immigrants worship. We find that places of worship are significant for physical health, social, emotional, spiritual, mental, and general quality of life amongst immigrants. The thesis is highly relevant in the current Canadian policy context, which includes contribution to the understanding of the determinants of health and integration of immigrants, providing insights into the concepts of sense of place and mental wellbeing, and broadening our understanding of African immigrants’ integration. Overall, this thesis develops a better understanding of immigrants’ settlement and integration, and further contributes to the broader immigration literature. Thesis Doctor of Philosophy (PhD) Employing an expanded meaning of the concept of sense of place within Health Geography, this thesis explores the relationship between sense of place and mental wellbeing of immigrants. The concept of sense of place demonstrates the importance of specific places for socioeconomic and health impacts on individuals and groups in their societies. While research has explored immigrants’ sense of place, few studies have attempted to explore visible minority’s perceptions of place and its influence on wellbeing. Using qualitative and quantitative techniques, this thesis explores the perceptions and experiences of place amongst Ghanaian and Somali immigrants in Hamilton, Ontario, Canada. First, we explore key informants’ revelations on immigrants’ sense of place and mental wellness in Hamilton, Ontario. Findings provide insight into the role of policies that affect determinants of health amongst immigrants. Second, we examine the effects of self-perceived mental wellness, socioeconomic and demographic variables on sense of place amongst Ghanaian and Somali immigrants living in Hamilton, based on an analysis of a survey questionnaire (n=236). Findings highlight a positive relationship between sense of place and mental wellness. Third, using descriptive and multivariate regression methods, we focus on factors that predict African immigrants’ life satisfaction in Canada. We examine sociodemographic, economic and health-related factors that predict life satisfaction amongst African immigrants, specifically Ghanaian and Somali immigrants. We find that immigrant settlement workers and agencies would be better able to meet the needs of immigrants if they are conscious of the factors that would empower immigrants to cope with life stresses. We suggest a reduction of stress by helping individuals and families identify sources of support, providing jobs, affordable housing, language interpretation and training. Lastly, we explore specific places, religious sites and their relationship to health and wellbeing for immigrants. Specifically, we explore churches and mosques where Ghanaian and Somali immigrants worship. We find that places of worship are significant for physical health, social, emotional, spiritual, mental, and general quality of life amongst immigrants. The thesis is highly relevant in the current Canadian policy context, which includes contribution to the understanding of the determinants of health and integration of immigrants, providing insights into the concepts of sense of place and mental wellbeing, and broadening our understanding of African immigrants’ integration. Overall, this thesis develops a better understanding of immigrants’ settlement and integration, and further contributes to the broader immigration literature.