Structural and functional characterisation of thyroid proteins involved in cancer, autoimmunity and hormone synthesis defects
Thyroid cancer is the most common endocrine malignancy and is often associated with auto-immunity and thyroid hormone synthesis impairment [1,2]. What is the molecular basis of this phenomenon? The successful PhD candidate will answer this outstanding question combining high-resolution cryo-EM structural analysis, bioinformatics, biochemistry and cellular studies. First, we will investigate structural epitopes and hormone synthesis defects in recombinant systems. Then, we will use assays in close-to-native thyroid cultures to characterise their implications in model cancerous cells . Finally, using samples from patients and bioinformatic analysis we will formulate a molecular model for the relationship among cancer, autoimmunity and hormone synthesis defects. This study will lay basis for alternative strategies to tackle these major thyroid diseases in vivo. Our laboratory is at the forefront of cryo-EM methodologies and molecular studies on thyroid hormone synthesis . We welcome motivated and creative students from any background interested in addressing long-standing problems in thyroid biology, using an integrative structural biology approach.
Please find more information at https://humantechnopole.it/en/research-groups/coscia-group/
Feel free to ask informal enquiries to: Francesca.coscia[at]fht.org
1.Fiore, E., Latrofa, F. & Vitti, P. Iodine, thyroid autoimmunity and cancer. Eur Thyroid J 4, 26–35 (2015).
2.Citterio, C. E., Targovnik, H. M. & Arvan, P. The role of thyroglobulin in thyroid hormonogenesis. Nat Rev Endocrinol 15, 323–338 (2019).
3.Antonica, F. et al. Generation of functional thyroid from embryonic stem cells. Nature 491, 66–71 (2012).
4.Coscia, F. et al. The structure of human thyroglobulin. Nature 578, 627–630 (2020).