Dishevelled (DVL) is the central hub of Wnt signal transduction that integrates and transduces upstream signals through distinct cytoplasmic cascades.
Looking at the many DVL faces reported in literature, three salient features underlying its function in signaling can be highlighted: (1) it interacts with more than seventy binding partners, (2) it is heavily phosphorylated at multiple sites by at least eight different kinases, in particular by Ck1δ/ε after Wnt stimulation, and (3) it consistently forms puncta in the cytosol, that are phase-separated self-assemblies also called liquid droplets.
Our working hypothesis is that DVL conformational plasticity mediated by the order-disorder interactions allows the combinatorial integration of phosphorylation input, partners binding, self-assembly in droplets, and allosteric coupling, to exquisitely control signal routing.
We integrate structural biology (NMR, X-ray, cryoEM) and biophysical techniques (FRET, ITC, BLI) with cellular readouts (TopFlash, BRET) and proteomics to understand DVL structure, function, and regulation.
Candidates can choose among three open questions, that if resolved, will have significant impact on Wnt research. 1) Does disorder provide new contexts to structured domain(s) and, hence, enhance the DVL functional space associated with them? 2) Is there a direction, order or hierarchy in the phosphorylation of individual S/T sites and clusters in DVL? 3) What are the physical behaviors associated with intrinsic disorder and their connection to DVL liquid‑liquid phase separation?
Your profile
- Must-have: MSc degree (preferably in Life Sciences) Strong interest in structural biology and biomolecular NMR applications. Experience in structural biology, biochemistry, and molecular biology methods English proficiency – oral and written Good communication and interpersonal skills, team player Motivation and curiosity-driven mindset Nice-to-have: Programming skills are a strong plus What we provide to you Open access to CEITEC MU core facilities with state-of-the‑art equipment and experienced staff Full‑time contract An attractive salary Flexible working hours Support for further education and professional development Benefits package: 6 weeks of paid holiday, medical insurance, financial contribution to meal and kindergarten/pension scheme, Multisport card, mental health care, sports lessons directly at the campus Kindergarten on Campus Support in these areas: Welcome Office service before and after arrival Grant Office support CEITEC PhD Committee CEITEC events – workshops, conferences, lectures, training, family gathering etc.