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Archiv-Übersicht     Angebot Nr. 13535

Angebotsdatum: 22. Juli 2019
Art der Stelle: Doktorarbeit
Fachgebiet: Biologie > Zellbiologie
Titel des Themas: Therapeutic melanoma growth repression by cyclic nucleotide inhibitor-loaded nanoparticles

Institut: Hautklinik
Adresse:
Dr. rer. nat. Christian Becker
Langenbeckstreasse 1
55131 Mainz
Tel.: 06131 172917   Fax.:
Bundesland: Rheinland-Pfalz
Homepage: http://https://www.researchgate.net/profile/Christian_Becker3/info/
E-Mail Kontakt: mail

Beschreibung: Nucleotide signaling molecules serve as universal regulators of metabolism and gene expression in all life forms. Within the immune system, increased intracellular levels of cyclic adenosine monophosphate (cAMP) uniformly repress immune cell function. We previously showed that regulatory T cells (Treg) use cAMP to suppress other immune cells (J. Exp. Med 2007). More recently, we observed increased intracellular cAMP levels in human and murine melanoma and showed that melanoma employ cAMP in order to metastasize and repress immune responses against them (Nat Immunol. 2018).
To interfere with melanoma cAMP formation therapeutically, we teamed up with chemists from Johannes Gutenberg-University Mainz to generate nanoparticles, which release an adenylyl cyclase (AC) inhibitor. Local application of such inhibitor-loaded particles significantly impaired melanoma growth through metabolic reprogramming of tumor tissue and induction of tumor immunity. In combination with partial depletion of Treg, AC-inhibitor-loaded particles achieved complete remission of established tumors (manuscript under review).
We currently further improve the cAMP inhibitor particles to make them systemically applicable and further investigate the molecular basis of cAMP-mediated reprogramming of human and murine immune cells in order to identify alternative, cell-specific intervention points.


We are looking for a highly motivated student with a masters/diploma degree in biology or biomedical chemistry and a solid background in immunology.

We offer excellent support, work in an exciting field of research, in a committed and friendly team and with national and international partners.

Methoden: mouse breeding and typing, animal experiments, immunological and molecular biological methods (e.g. flow cytometry, in vivo imaging, single cell NGS etc.)
Anfangsdatum: 22. Juli 2019
Geschätzte Dauer: 3 Jahre
Bezahlung: TVL E13 65%
Papers: Bohn T, Rapp S, Luther N, Klein M, Bruehl TJ, Kojima N, Aranda Lopez P, Hahlbrock J, Muth S, Endo S, Pektor S, Brand A, Renner K, Popp V, Gerlach K, Vogel D, Lueckel C, Arnold-Schild D, Pouyssegur J, Kreutz M, Huber M, Koenig J, Weigmann B, Probst HC, von Stebut E, Becker C, Schild H, Schmitt E, Bopp T.
Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages.
Nat Immunol. 2018 Dec;19(12):1319-1329

Birke A, Huesmann D, Kelsch A, Weilbächer M, Xie J, Bros M, Bopp T, Becker C, Landfester K, Barz M. Polypeptoid-block-polypeptide copolymers: synthesis, characterization, and application of amphiphilic block Copolypept(o)ides in drug formulations and miniemulsion techniques.
Biomacromolecules. 2014 Feb 10;15(2):548-57

Weilbächer M, Allmeroth M, Hemmelmann M, Ritz S, Mailänder V, Bopp T, Barz M, Zentel R, Becker C. Interaction of N-(2-hydroxypropyl)methacrylamide based homo, random and block copolymers with primary immune cells.
J Biomed Nanotechnol. 2014 Jan;10(1):81-91


Bacher N, Raker V, Hofmann C, Graulich E, Schwenk M, Baumgrass R, Bopp T, Zechner U, Merten L, Becker C, Steinbrink K. Interferon-α suppresses cAMP to disarm human regulatory T cells.
Cancer Res. 2013 Sep 15;73(18):5647-56.

Klein M, Vaeth M, Scheel T, Grabbe S, Baumgrass R, Berberich-Siebelt F, Bopp T, Schmitt E, Becker C. Repression of cyclic adenosine monophosphate upregulation disarms and expands human regulatory T cells.
J Immunol. 2012 Feb 1;188(3):1091-7

Bopp T, Becker C, Klein M, Klein-Hessling S, Palmetshofer A, Serfling E, Heib V, Becker M, Kubach J, Schmitt S, Stoll S, Schild H, Staege MS, Stassen M, Jonuleit H, Schmitt E. Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression.
J Exp Med. 2007 Jun 11;204(6):1303-10



Sonstiges: To apply, send a single PDF file containing a CV with contact information, and a statement outlining your research interests and relevant work experience, contact for recommendation.

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