Cookie Settings

We use cookies to optimize our website. These include cookies that are necessary for the operation of the site, as well as those that are only used for anonymous statistic. You can decide for yourself which categories you want to allow. Further information can be found in our data privacy protection .

Essential

These cookies are necessary to run the core functionalities of this website and cannot be disabled.

Name Webedition CMS
Purpose This cookie is required by the CMS (Content Management System) Webedition for the system to function correctly. Typically, this cookie is deleted when the browser is closed.
Name econda
Purpose Session cookie emos_jcsid for the web analysis software econda. This runs in the “anonymized measurement” mode. There is no personal reference. As soon as the user leaves the site, tracking is ended and all data in the browser are automatically deleted.
Statistics

These cookies help us understand how visitors interact with our website by collecting and analyzing information anonymously. Depending on the tool, one or more cookies are set by the provider.

Name econda
Purpose Statistics
External media

Content from external media platforms is blocked by default. If cookies from external media are accepted, access to this content no longer requires manual consent.

Name YouTube
Purpose Show YouTube content
Name Twitter
Purpose activate Twitter Feeds

Division of Immune Diversity

Prof. Dr. Nina Papavasiliou

Unlike most other cell types in the body, which are static, immune cells must travel through (and adapt to) multiple different environments on a constant basis. This ability to adapt is predicated on molecular mechanisms that generate informational diversity, such that every immune cell is genetically different that every other (which is the case with cells of the adaptive immune system, such as B and T lymphocytes) or transcriptomically different than their siblings (which appears to be the case with inmate immune cells, such as cells of the monocytic lineage). Overall, the goal of our research is to understand the molecular processes that generate phenotypic diversity, which in turn is required for adaptation.
This interest originally directed my lab's work to DNA diversification in the context of the adaptive immune response, specifically to mechanisms that direct DNA mutation to antibody genes in the germinal center. This process, which depends on AID-mediated DNA deamination followed by error prone repair, generates immunoglobulin sequence diversity and underlies affinity maturation of the antibody response.
More recently, my lab has begun studying population diversity in the context of the innate immune response, as it is generated by rampant but targeted RNA editing (an "active" form of mutation, which depends on expression of the editing deaminases APOBEC1 or ADAR, and which unlike DNA mutation does not leave a mark on the genome). For these studies we developed new tools that took advantage of next generation sequencing to generate custom bioinformatic approaches within the lab, as well as mathematical modeling to deconvolute RNA editing as it occurs in single cells, to generate heterogeneous populations with an increased capacity to adapt to changes in the environment.
Finally, we have an active interest in the regulation of coat protein diversification in parasites (specifically, the African trypanosome T.brucei), which appears to be mechanistically similar to Ig diversification. To answer long-standing questions in this field, we have taken advantage of our work in immunology and bioinformatics, to (1) import new tools to study the initiation of VSG diversification in vitro and to (2) generate new approaches to study VSG diversity at the population level in vivo both in terms of sequence diversity and in terms of antigenic plurality. Overall, this aspect of our work should provide a robust (and generalizable) mechanistic understanding of a changing antibody response toward an antigenic coat that changes just as rapidly, and their co-evolution through time.

We are very interested in understanding the role of DNA mutation and RNA editing in the generation of proper immune repertoires; and are also keen on understanding how these mechanisms, that have evolved to generate immune diversity, are co-opted in the context of tumours to help them evolve resistance. We are interested in understanding relapse from a clinical perspective, as well as through in vitro proof-of-principle studies.

Contact

Prof. Dr. Nina Papavasiliou
Immune Diversity (D150)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 (0)6221 421390

Selected Publications

  • BR Rosenberg, CE Hamilton, MM Mwangi, S Dewell, F. N. Papavasiliou. 2011. Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing targets in transcript 3' UTRs. Nat Struct Mol Biol. 18(2):230-6.
  • MR Mugnier, GAM Cross, F. N. Papavasiliou. 2015. The in vivo dynamics of antigenic variation in Trypanosoma brucei. Science 347(6229):1470-3
  • D Harjanto, T Papamarkou, V Rayon-Estrada, A. Papavasiliou, F. N. Papavasiliou. 2016. RNA editing generates cellular subsets with diverse sequence within populations. Nature Communications 7:12145.
  • Hovel-Miner G, Mugnier MR, Goldwater B, Cross GA, Papavasiliou FN. 2016. A Conserved DNA Repeat Promotes Selection of a Diverse Repertoire of Trypanosoma brucei Surface Antigens from the Genomic Archive. PLoS genetics 12(5):e1005994.
to top
powered by webEdition CMS