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Projects / Programmes source: ARIS

Differences Between Mouse And Human Endosomal Immune Response Pathway: Crystal Structures Of Protein Complexes and their Analysis

Research activity

Code Science Field Subfield
1.05.00  Natural sciences and mathematics  Biochemistry and molecular biology   

Code Science Field
P310  Natural sciences and mathematics  Proteins, enzymology 
Keywords
Immune response; regulation; Proteases; Imhibitors; human ; mouse ; cysteine cathepsins;
Evaluation (rules)
source: COBISS
Researchers (2)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  04988  PhD Dušan Turk  Biochemistry and molecular biology  Head  2008 - 2011  622 
2.  29883  Nina Vidergar  Biochemistry and molecular biology  Researcher  2008 - 2011  10 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,767 
Abstract
We plan to reveal the differences and similarities of proteolytic pathways of endosomal immune system responses from human and mouse and thereby assist the drug discovery process of diseases associated with human immune system in which mice usually serve as animal models. The proposed research covers a part only: determination and analysis of crystal structures of the proteins building the core of the endosomal antigen presentation machinery: proteases, protease inhibitors and MHC class II molecules. The proteases studied will be human and mouse cysteine cathepsins B, L, S, K, V, F, C and some others when they become available, whereas the inhibitor list contains stefins, cystatins and inhibitory fragment of p41 form of MHC class II associated invariant chain. The immediate goal is the determination of crystal structures of complexes from human and their counterparts from mice. The longer-term goal is to build a system, which will enable us to expose and predict similarities and differences of human and mice MHC class II antigen presentation machinery during antigenic protein degradation.
Significance for science
The esearch is strategic basic research targeting a very present problem in our human society – defense against infectious and auto immune diseases. By revealing the players and differences between human and mouse immune responses is a very important for the drug discovery. The derived results thus have the potential to become of world-wide relevance, which is important for promotion of the Slovenia and preservation of the structural biology in the country. Understanding the immune response is one of the currently most emphasized research areas in biomedical sciences. Mouse is the major animal model used in these investigations, thereby the gained knowledge may become extremely useful and is crucial for setting up the preclinical investigations - to understand when the mouse model is adequate and when not. Obtained results as well as methodologies used should be useful for any pharmaceutical company, including those present in Slovenia.
Significance for the country
Work within this project is performed within the working environment of the Structural biology program, which is collaborating with a number of groups inside and outside the country. The group is the core of infrastructural program “Centre for protein and structure production” and coordinates the “Centre of excellence for integrated approaches in chemistry and biology of proteins”. Both Centres already do and will provide support for a number of groups in the country and near vicinity. The working group is a potential source of highly qualified personal that is needed in modern biotechnology oriented industry. Qualified personal has the potential to start their independent industrial career in the area of molecular biology, biotechnology and agriculture. PhD in natural sciences is also the basic education for patent lawyers.
Most important scientific results Annual report 2008, 2009, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2008, 2009, final report, complete report on dLib.si
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