Short Elective Modules

Short Elective Modules for Master's students in Biomedical Sciences
Module slot I: 22.4. - 10.5.2013 (closed)
Moduel slot II: 13.5. - 31.5.2013 (closed)


Project 1: Intestinal microbial composition imprints the regulation of immunoglobulin E (Prof. McCoy & Dr. Cahenzli)
Summary:
Intestinal microbes are true educators of the immune system. Following birth, the bacteria colonizing our intestine system engage in a crosstalk with the immune system, which ensures intestinal homeostasis. The postnatal environment influences intestinal microbial composition thereby rendering each individual microbially unique and possibly immunologically unique. To experimentally address the role of intestinal microbial composition on baseline immune regulation, our laboratory makes use of mice kept under strict and defined hygiene conditions, germ-free or Altered Schaedler Flora (ASF). Germ-free mice are completely devoid of microbes whereas ASF mice are associated with eight defined bacterial species. These mice are then compared with mice harboring an undefined and diverse microflora (SPF). Similar to healthy non-atopic individuals, total serum IgE levels are very low in SPF mice. However, germ-free mice and some ASF mice fail to maintain such low baseline IgE levels. Thus in the absence of threshold bacterial stimuli IgE levels become abnormally elevated, suggesting that the regulatory pathway that maintains IgE at basal levels is disrupted. We hypothesize that in the absence of threshold microbial stimuli the immune system is not adequately educated, which in turn results in immune dysregulation reflected by abnormally high levels of IgE. 
To elucidate the pathway that leads to this immune dysregulation, we will compare the gene expression of key cytokines between SPF mice and germ-free mice. This will be achieved using real time PCR, which involves RNA extraction, cDNA synthesis and then quantitative PCR.
These studies should reveal the impact of microbial composition in shaping the baseline immune regulation and may give insights into why there has been an increase in diseases associated with immune dysregulation, such as atopic allergy or autoimmunity.

Requirements:
Students selecting this module should be interested in immunology and more particularly on the impact of intestinal microbes on the maturation and regulation of the immune system.

Literature:
McCoy et al. Natural IgE production in the absence of MHC Class II cognate help. Immunity (2006) vol. 24 (3) pp. 329-39
Smith et al. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol (2007) vol. 19 (2) pp. 59-69
Macpherson et al. Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria. Immunology (2005) vol. 115 (2) pp. 153-62

Time-slots & # of students:
Elective module series I : 1 student
Elective module series II: 1 student

Location:
Department of Clinical Research
Mucosal Immunology Lab
Murtenstrasse 35
CH-3010 Bern

Contact:
Prof. Kathy McCoy
phone: 031 632 0931
e-mail: kathleen.mccoy (at) dkf.unibe.ch


Project 2: Mucosal immunity and the microbiota (Prof. Macpherson, Dr. Lawson, Dr. Li Hai)
Summary:
Mammals are colonized with intestinal bacteria from the time of birth. Our health is dependant on the successful establishment and maintenance of a peaceful an d mutualistic relationship with this large bacterial burden. A major focus of our lab is to investigate the mechanisms that ensure host-microbial homeostasis. Upon bacterial intestinal colonization the regulation and expression of many immune factors are altered, with specific induction of large amounts of immunoglobulin A (IgA). This IgA is specific to intestinal bacteria and is secreted across the intestinal epithelium where it can bind to bacteria in the lumen of the gut.  We are investigating the interaction between IgA and intestinal bacteria with the aim to determine the exact role that IgA plays in host-microbial homeostasis.  By specifically colonizing antibody-sufficient and -deficient germ-free mice (which are devoid of all microorganisms) with single bacterial species we have found that IgA affects bacteria by controlling their mutation rate and enhancing the rate bacteria are shed from the gut.  Common techniques used to analyze these interactions are bacterial plating, spectrometry, microscopy, ELISA and flow cytometry.   Our present research focuses to further our understanding in why we produce such specific IgA and its function in maintaining a truly mutualistic relationship with our intestinal bacteria.

Requirements:
Students selecting this module should be interested in both microbiology and immunology, and learning how to analyze bacteria kinetics using both culture independent and dependent techniques.

Literature:
Macpherson et al. Curr Opin Gastroenterol. (2011) vol. 27 (6) pp. 529-533
Hapfelmeier et al. Science (2010) vol. 328 (5986) pp. 1705-1709

Time-slots & # of students:
Elective module series I : 1 student
Elective module series II: 1 student

Location:
Department of Clinical Research
Mucosal Immunology Lab
Murtenstrasse 35
CH-3010 Bern

Contact:
Prof. Andrew Macpherson
phone: +41 (0) 31 632 80 25
e-mail: Marie-Louise.Zbinden (at) insel.ch


Project 3: Antigen-specificity of intestinal regulatory T cells (Dr. Geuking)
Summary:
We harbor 10 times more bacteria in our intestines than the total number cells in our own body. To ensure a healthy co-existence with these bacteria we have evolved to establish a mutualistic relationship with the intestinal microbiota. This mutualism is important to maintain homoestasis and prevent unwanted inflammatory reactions towards the intestinal microbiota that could lead to inflammatory bowel diseases (IBD) such as Crohn’s disease or ulcerative colitis. The immunological adaptations that occur in response to intestinal colonization are crucial to establish and maintain mutualism. We have recently shown that activation of intestinal regulatory T cells is a crucial adaption in response to colonization to prevent activation of effector CD4 T cells. We are now investigating whether the regulatory T cells that are activated carry T cell receptors that are specific for the commensal mcirobiota. To do this we are generating recombinant E.coli strains that express certain model T helper cell epitopes. The generation of this bacterial strains requires microbiological and molecular biological techniques whereas evaluation of the immunological consequences will be assessed by flow cytometry.

Requirements:
Ideally, students selecting this module are interested both microbiology and immunology. The methods also require a good understanding of molecular biology.

Literature:
Geuking MB et al., Intestinal Bacterial Colonization Induces Mutualistic Regulatory T Cell Responses. Immunity 2011 May 27;34(5):794-806.
Macpherson, A.J. et al.,. Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria. Immunology 2005 115:153-162.

Time-slots & # of students:
Elective module series I : 1 student (student appointed)
Elective module series II: 1 student

Location:
Department of Clinical Research
Mucosal Immunology Lab
Murtenstrasse 35
CH-3010 Bern

Contact:
Dr. Markus Geuking
phone: 031 632 49 73
e-mail: geuking (at) dkf.unibe.ch

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