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Archiv-Übersicht     Angebot Nr. 13953

Angebotsdatum: 27. Juli 2020
Art der Stelle: Doktorarbeit
Fachgebiet: Humanmedizin > Sonstiges
Titel des Themas: 1. Topic: Identification of isoenzyme-specific inhibitors of Deiodinase 1; 2. Topic: Evaluating DIO-steered T3-dependent modulation of lipid metabolism-related gene expression.

Institut: Institut für Experimentelle Endokrinologie
Adresse:
Prof. Josef Köhrle
Augustenburger Platz 1
13353 BERLIN
Tel.:    Fax.:
Bundesland: Berlin
Homepage: http:// https://expendo.charite.de/en
E-Mail Kontakt: mail

Beschreibung: 2 PhD Positions (E13, 65%) are available in the newly established DFG Transregio CRC/TR 296 “Local control of TH action” (LocoTact) from 01.08.2020 (or later) for at least 3.5 years in the teams of Prof. Köhrle and Dr. E.K. Wirth.
The active thyroid hormone T3, generated and degraded by deiodinase isoenzymes, is a key regulator of hepatic lipid metabolism.
We aim to elevate local T3 concentrations by steering activities of T3-degrading deiodinase isozymes.
The following research goals will be addressed by our team in close cooperation:
1. Identification of isoenzyme-specific inhibitors of Deiodinase 1 (DIO1) by high throughput screening (HTS) in cooperation with FMP Berlin.
2. in vitro testing of DIO1 inhibitors in primary THAI mouse hepatocytes.
3. Establishing T3-sensitive hiPSC-derived TH-reporter cells.
4. Evaluating DIO-steered T3-dependent modulation of lipid metabolism-related gene expression.
Goals 1. and 2 will be the focus for one PhD project, goals 3. and 4. for the second one.
Methoden: Techniques that will be applied throughout the projects include DNA, RNA and protein extraction, enzyme activity assays, PCR, gene expression analysis, cell culture, and work with laboratory mice.
Hands on experience in cell culture and biochemical analytics, especially molecular and cell biology techniques and a thorough knowledge of physiology and genetics are advantageous.
Solid basic experience in scientific data handling, documentation and management is of advantage.
A FELASA B certification would be beneficial.
Anfangsdatum: 27. Juli 2020
Geschätzte Dauer: 3.5 years
Bezahlung: 65% E13
Papers: Renko K, … Köhrle J, et al. (2015) An improved non-radioactive screening method identifies genistein and xanthohumol as potent inhibitors of iodothyronine deiodinases. Thyroid 2015;25:962-8.

Köhrle J, et al. (2020) 3,5-T2 – A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine And Intracrine Hepatic Action. Frontiers in Endocrinology, Thyroid Endocrinology. doi: 10.3389/fendo.2019.00787

Kortenkamp A, …, Frädrich C, … Köhrle J, et al. (2020) Removing critical gaps in chemical test methods by developing new assays for the identification of thyroid hormone system-disrupting chemicals – the ATHENA project. Ijms 21 (9) 10.3390/ijms21093123
Sonstiges: The applicants should hold a Master’s degree (or a comparable Diploma) in Biology, Biochemistry, Molecular Life Science or similar and should be able to communicate in English.

PhD students are expected to compile and present their results and project achievements at regular lab meetings and CRC workshops.

The PhD students will be enrolled into the integrated CRC-TR graduate school with a specific and exciting educational curriculum in addition to the laboratory work, including courses at our partner sites in Essen and Lübeck.

Our basic-translational thyroid hormone research is focussed on energy and lipid metabolism and also embedded into a related Ho2020-funded EU
consortium (ATHENA) addressing the role of thyroid hormones in brain development.

Willingness to work in an interdisciplinary research team in cooperative spirit is highly appreciated.
High motivation, scientific interest in endocrine-oriented research and good communication skills will markedly facilitate timely completion of these two challenging PhD projects.
We expect openness for constructive interactions with our partner teams at all three CRC sites.

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