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1/ Few years ago, we reported the identification of the novel #ECM protein SNED1 a promoter of mammary tumor metastasis @eLife elifesciences.org/articles/01308
2/ SNED1 became #MyFavoriteProtein, but what do you do when almost nothing is known about your new favorite protein?
3/ Only 1 thing: roll up your sleeves, assemble a great team, be in a supporting environment @UICPhysiology @kitaj_angio and get started! Along the way, we are sharing our results on @biorxivpreprint, so feedback and comments are welcome!
Here is what we have learned so far:
4/ 1st, we generated a Sned1 KO mouse and found that the global deletion of Sned1 led to perinatal lethality. The few KO that survived were smaller in size and presented severe cranio-facial defects: biorxiv.org/content/10.110…
5/ Using the LacZ reporter gene to assess the activity of Sned1 promoter, we found that Sned1 is broadly expressed during development, in particular in neural-crest-cell derivatives and in the somites.
6/ We hypothesized that Sned1 may regulate NCC phenotype, so we generated an NCC-specific Sned1 KO mouse, which validated our hypothesis!
7/ SNED1 is located on 2q37.3, and 2q37.3 deletion-syndrome patients present with cranio-facial malformations. Much more to be done on that front, but a pretty interesting observation!
8/ In order to gain molecular insights, we also conducted an in-depth structural analysis and attempted to draft the first models for SNED1 and one of its domain, the NIDO domain, only found in 5 proteins in the human proteome (how cool!) biorxiv.org/content/10.110…
9/ We also used molecular modeling to predict SNED1's domain- and protein-level interactomes and are gearing up to validate these interactions experimentally as soon as the lab fully reopens!
10/ We have come a long way but still have a long way to go! While these studies are mostly descriptive, they are needed to help us eventually decipher the cellular & molecular mechanisms by which SNED1 exerts its function in development and cancer.
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