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DESH BANDHU GANGWAR presentation on Somatic hypermutation


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DESH BANDHU GANGWAR presentation on Somatic hypermutation

  2. 2. Contents<br />1-Introduction<br />2-Molecules involve in SHM<br />3-Model of SHM<br />4-Future Directions<br />
  3. 3. Introduction<br />somatic hypermutation (SHM) is a diversity generating, regulated cellular mechanism displayed by the adaptive immune response.<br />Somatic Hypermutation adds diversity in already Rearranged Gene Segments.<br />Somatic hypermutation occurs at a frequency of<br /> 10¯3/base pair/ generation, than the spontaneous mutation rate about 10⁻8/bp/generation.<br />
  4. 4. This Rate is higher hence the name, hypermutation.<br />These mutations occur mostly at “hotspots” in the DNA, known as hypervariable regions. <br />These regions correspond to the complementarity determining regions, the sites involved in antigen recognition on the antibody.<br />
  5. 5. These mutation result from nucleotide substitution rather than addition or deletion.<br />They influence the process of affinity maturation of B cells.<br />Affinity maturation leads to increase the affinity of antibodies for a particular antigen.<br />
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  8. 8. Molecules involved in SHM<br />IgM antibodies expressing V regions that have undergone SHM, as well as IgG and IgA antibodies with no somatic mutations.<br />Activation-induced cytidinedeaminase: A<br /> B cell-specific protein required for SHM.<br />Uracil N-glycosylase: Removing uracil generated by AID deamination.<br />
  9. 9. Mismatch repair proteins: Mismatch repair (MMR) normally maintains genomic integrity.<br />MMR eliminates mutations that arise spontaneously in the genome.<br />Error-prone DNA polymerases: increase mutation rate.<br />
  10. 10. Model of somatic hypermutation<br />
  11. 11. Future directions<br /><ul><li> Evolving protein in mammalian cell using SHM</li></ul> SHM cell with the target gene integrated in the genome<br /> cell population with the target gene mutated <br /> cells with the desired phenotype<br /> amplified cells with the desired phenotype<br /> isolate and characterize<br />
  12. 12. SHM Plateform<br />
  13. 13. To Produce New Fluorescent Proteins<br />Tsien’s group has cloned a red fluorescent protein (RFP) into human B-cells and allowed them to make variants that could then be isolated based on their colors by flow-cytometry.<br />
  14. 14. Questions??<br />