KdPT is a tripeptide structurally related to the C-terminal amino acids of alpha-melanocyte-stimulating hormone, which was previously shown to exhibit anti-inflammatory effects in various inflammatory diseases. However, due to its unfavourable physical and chemical properties KdPT is for instance not suitable for topical application. Hence, KdPT was modified to improve its physical and chemical properties. To analyze the effect of the KdPT derivatives, phenotype, function and migratory activity will be analyzed in primary mouse immune cells by multicolor flow cytometry, multiplex bead assays or quantitative PCRs. Furthermore, the effect of the anti-inflammatory tripeptide on mouse endothelial cells will be analyzed by performing immunofluorescence staining and (if time is available) and transendothelial electrical resistance (TEER) assays.
Seminar:
- Presentation and discussion of laboratory methods used in the practical part
- Basic knowledge in immunology and immune cell subsets
- Role of aryl hydrocarbon receptor signaling in immunology and immune therapy
- Role of dendritic cells during antigen presentation and bridging innate and adaptive immunity
Exercise:
This module involves working on small research projects. The projects include basic immunology with the goal to better understand the phenotype and function of dendritic cells as well as possibilities to modulate their maturation, activation and antigen presenting capacity.
Practical part:
During infection, bacteria, such as Yersinia enterocolitica, can actively translocate anti-inflammatory proteins into the host cell cytoplasm to suppress the host immune response. These proteins can be produced recombinantly and are to be formulated as drugs for therapy. For this purpose, the mouse model of imiquimod-induced psoriasis-like skin inflammation was used, and the animals were treated with the bacterial compounds. After the efficacy has been proven based on the reduction in disease severity, the mechanism of action shall be analyzed in detail. For this purpose, the induction of apoptosis, the inflammasome activation, cytokine production and NF-B activation or the effect of the proteins on the integrity of the epithelial barrier will be analyzed within this research module. Methods such as multicolor immunofluorescence, multiplex assays for cytokine quantification and characterization of signaling cascades, RNA sequencing or kinome analysis will be used.
Theoretical part (seminar):
During the research module, the pathomechanisms of chronic inflammatory skin diseases will be discussed, with a specific focus on the involvement of the immune system in the development of psoriasis vulgaris. At the same time, various possibilities how bacterial pathogens evade host immune defenses will be presented. These possibilities include the production of cell-penetrating peptides (CPEs) with anti-inflammatory properties, which can be developed as agents for therapy (drugs-from-bugs concept).
Practical part:
During infection, bacteria, such as Yersinia enterocolitica, can actively translocate anti-inflammatory proteins into the host cell cytoplasm to suppress the host immune response. These proteins can be produced recombinantly and are to be formulated as drugs for therapy. For this purpose, the mouse model of imiquimod-induced psoriasis-like skin inflammation was used, and the animals were treated with the bacterial compounds. After the efficacy has been proven based on the reduction in disease severity, the mechanism of action shall be analyzed in detail. For this purpose, the induction of apoptosis, the inflammasome activation, cytokine production and NF-B activation or the effect of the proteins on the integrity of the epithelial barrier will be analyzed within this research module. Methods such as multicolor immunofluorescence, multiplex assays for cytokine quantification and characterization of signaling cascades, RNA sequencing or kinome analysis will be used.
Theoretical part (seminar):
During the research module, the pathomechanisms of chronic inflammatory skin diseases will be discussed, with a specific focus on the involvement of the immune system in the development of psoriasis vulgaris. At the same time, various possibilities how bacterial pathogens evade host immune defenses will be presented. These possibilities include the production of cell-penetrating peptides (CPEs) with anti-inflammatory properties, which can be developed as agents for therapy (drugs-from-bugs concept).
KdPT is a tripeptide structurally related to the C-terminal amino acids of alpha-melanocyte-stimulating hormone, which was previously shown to exhibit anti-inflammatory effects in various inflammatory diseases. However, due to its unfavourable physical and chemical properties KdPT is for instance not suitable for topical application. Hence, KdPT was modified to improve its physical and chemical properties. To analyze the effect of the KdPT derivatives, phenotype, function and migratory activity will be analyzed in primary mouse immune cells by multicolor flow cytometry, multiplex bead assays or quantitative PCRs. Furthermore, the effect of the anti-inflammatory tripeptide on mouse endothelial cells will be analyzed by performing immunofluorescence staining and (if time is available) and transendothelial electrical resistance (TEER) assays.
Seminar:
- Presentation and discussion of laboratory methods used in the practical part
- Basic knowledge in immunology and immune cell subsets
- Role of aryl hydrocarbon receptor signaling in immunology and immune therapy
- Role of dendritic cells during antigen presentation and bridging innate and adaptive immunity
Exercise:
This module involves working on small research projects. The projects include basic immunology with the goal to better understand the phenotype and function of dendritic cells as well as possibilities to modulate their maturation, activation and antigen presenting capacity.
Practical part:
During infection, bacteria, such as Yersinia enterocolitica, can actively translocate anti-inflammatory proteins into the host cell cytoplasm to suppress the host immune response. These proteins can be produced recombinantly and are to be formulated as drugs for therapy. For this purpose, the mouse model of imiquimod-induced psoriasis-like skin inflammation was used, and the animals were treated with the bacterial compounds. After the efficacy has been proven based on the reduction in disease severity, the mechanism of action shall be analyzed in detail. For this purpose, the induction of apoptosis, the inflammasome activation, cytokine production and NF-B activation or the effect of the proteins on the integrity of the epithelial barrier will be analyzed within this research module. Methods such as multicolor immunofluorescence, multiplex assays for cytokine quantification and characterization of signaling cascades, RNA sequencing or kinome analysis will be used.
Theoretical part (seminar):
During the research module, the pathomechanisms of chronic inflammatory skin diseases will be discussed, with a specific focus on the involvement of the immune system in the development of psoriasis vulgaris. At the same time, various possibilities how bacterial pathogens evade host immune defenses will be presented. These possibilities include the production of cell-penetrating peptides (CPEs) with anti-inflammatory properties, which can be developed as agents for therapy (drugs-from-bugs concept).
Practical part:
During infection, bacteria, such as Yersinia enterocolitica, can actively translocate anti-inflammatory proteins into the host cell cytoplasm to suppress the host immune response. These proteins can be produced recombinantly and are to be formulated as drugs for therapy. For this purpose, the mouse model of imiquimod-induced psoriasis-like skin inflammation was used, and the animals were treated with the bacterial compounds. After the efficacy has been proven based on the reduction in disease severity, the mechanism of action shall be analyzed in detail. For this purpose, the induction of apoptosis, the inflammasome activation, cytokine production and NF-B activation or the effect of the proteins on the integrity of the epithelial barrier will be analyzed within this research module. Methods such as multicolor immunofluorescence, multiplex assays for cytokine quantification and characterization of signaling cascades, RNA sequencing or kinome analysis will be used.
Theoretical part (seminar):
During the research module, the pathomechanisms of chronic inflammatory skin diseases will be discussed, with a specific focus on the involvement of the immune system in the development of psoriasis vulgaris. At the same time, various possibilities how bacterial pathogens evade host immune defenses will be presented. These possibilities include the production of cell-penetrating peptides (CPEs) with anti-inflammatory properties, which can be developed as agents for therapy (drugs-from-bugs concept).
as defined in the admission and examination regulations
Further information
Module Capacity: unrestricted
Method of assesment
graded: project report
ungraded: participation in seminar and 30 min. presentation
Exam dates
Will be announced at the beginning of the module
Learning outcomes/competencies
Competencies:
++ deepened biological and / or clinical expertise
++ deepened knowledge of biological working methods and / or clinical diagnostics
++ data analysis skills
+ interdisciplinary thinking
++ critical and analytical thinking
++ independent searching and knowledge of scientific literature
++ ability to perform independent biological research
++ data presentation and discussion (written and spoken)
+ team work
+ ethics and professional behaviour
+ project and time management