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Archiv-Übersicht     Angebot Nr. 12521

Angebotsdatum: 9. August 2018
Art der Stelle: Doktorarbeit / Diplomarbeit
Fachgebiet: Biologie > Mikrobiologie
Titel des Themas: Protein folding in vitro and in vivo

Institut: Molecular, Cellular and Developmental Biology
Herr James C.A. Prof. Bardwell
830 N. University Ave
48109 Ann Arbor
Tel.:    Fax.:
Homepage: http://https://sites.lsa.umich.edu/bardwell-lab/
E-Mail Kontakt: mail

Beschreibung: We investigate protein folding both in vitro and in vivo. Our goal is to understand protein folding on a level so that we can manipulate it. Using genetic selection strategies, we study how cells deal with protein folding stress.

We have developed protein folding biosensors that combine the stability of a protein directly with antibiotic resistance. This allows us to optimize protein folding in the cell (1) and discover new folding factors (2). Protein folding in the cell is dependent on folding helpers, such as protein disulfide isomerases and chaperones. We investigate the mechanisms of these folding helpers in vivo and in vitro by means of genetic, biochemical, biophysical and structural biology methods in bacteria as well as in yeast (2,3,4,5,6,7,8). One of these new folding factors is the molecular chaperone Spy (2). Recently, we kinetically and structurally characterized the mechanism by which Spy supports protein folding. Spy accommodates an amphiphilic "folding-friendly" surface, to which proteins bind and fold. Our hypothesis that other chaperones use a similar mechanism to help proteins fold is currently being tested in various other recently discovered chaperones.

We are looking for highly motivated PhD students with a Master's or equivalent degree in Molecular Biology / Genetics / Biotechnology / Biochemistry / Biophysics who are interested in protein folding.

Our doctoral students generally complete research in our laboratory after 3 years of research. The annual income of a doctoral student is $ 30,000US.

We also offer the opportunity for students to complete their master's or master's thesis or a research internship of 3 to 12 months in length.

We are also looking for Postdocs!

We have a lot of experience with German students and offer assistance for visas, apartments, etc.

Our lab is located at the University of Michigan, one of the top 5 public universities in the US that offers an excellent environment for research.


Methoden: Standard biophysical and biochemical methods of protein biochemistry; molecular cloning; protein expression in E.coli and yeast; Western Blotting; NMR; cristallography; genetic screens and selections
Anfangsdatum: 1. Oktober 2018
Geschätzte Dauer: 3-4 Jahre
Bezahlung: ~ $33 000
Papers: 1. Foit L et al (2009) Optimizing protein stability in vivo. Mol Cell 36: 861-871.
2. Quan et.al. (2011) Genetic selection designed to stabilize proteins uncovers a
chaperone called Spy. Nature Struct. Mol. Biol.18(3):262-9
3. Foit L et al. (2011) Chaperone activation by unfolding. PNAS 110(14):E1254-62.
4. Quan S et al. (2014) Super Spy variants implicate flexibility in chaperone action. Elife.3:e01584.
5. Stull F et al. (2016). Substrate protein folds while it is bound to the ATP-independent chaperone Spy. Nature Struct. Mol. Biol. 23(1):53-8.
6. Docter BE et al. (2016). Do nucleic acids moonlight as molecular chaperones? Nucleic Acids Res. 44(10):4835-45.
7. Horowitz S, et al. (2016). Visualizing chaperone-assisted protein folding. Nature Struct. Mol. Biol. 23(7):691-7.
8. Koldewey P et al. (2016). Forces Driving Chaperone Action. Cell 166(2):369-79.
Sonstiges: Starting date is flexible but ideally as soon as possible.