A postdoctoral position is available in the Kriwacki lab for solution NMR studies of protein complexes involved in regulation of cell division and apoptosis.
One project focuses on the cyclin-dependent kinase (Cdk) inhibitors, p27 and p21, bound to Cdk/cyclin complexes. Recent studies have shown that p27 is phosphorylated by oncogenic tyrosine kinases and that tyrosine phosphorylation alters the structure and function of p27 that is bound to Cdk2/cyclin A. We seek to understand (using NMR) the role of protein dynamics in modulating the accessibility of p27 to tyrosine kinases and in modulating the influence of p27 on the activity of Cdk2 [see Galea, et al., Biochemistry, 47:7598, 2008; Dunker & Uversky, Nat. Chem. Biol., 4:229, 2008; Grimmler, et al., Cell, 128:269, 2007; Lacy, et al., Nat. Mol. Struct. Biol., 11:358, 2004].
A second project centers on proteins involved in apoptotic signaling, specifically PUMA, BCL-xL and p53. BCL-xL binds and inactivates the pro-apoptotic activity of p53. However, when activated in response to DNA damage, PUMA binds to BCL-xL, releasing and activating p53 and inducing apoptosis [see Chipuk, et al., Science, 309:1732, 2005]. In work in preparation for publication, we have demonstrated that PUMA induces drastic structural remodeling of BCL-xL, providing a mechanism for p53 release. We seek to understand the role of protein dynamics in PUMA-induced remodeling of BCL-xL using NMR spectroscopy. Further, we are using NMR to study the p53/BCL-xL complex that is disrupted by PUMA.
The NMR lab at St. Jude houses Bruker 600 & 800 MHz spectrometers equipped with cryoprobes. In addition, a wide variety of other biophysical instruments are available within the department and institutional core facilities, providing opportunities for multidisciplinary training.
Candidates with recent PhD or MD degrees are encouraged to apply. A strong background in protein NMR spectroscopy is preferred, and experience with molecular biology, protein biochemistry and biophysics would be advantageous. Please send a CV, a brief statement of research interests, and the names of three references to:
Richard W. Kriwacki
Department of Structural Biology/MS311
St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678