WEHI PhD Completion Seminar hosted by Professor Sandra Nicholson

Grace Bidgood

PhD Student – Nicholson Laboratory, Inflammation division, WEHI

Nuclear localisation of SOCS1 occurs via the importin-α KPNA6 and is required for regulation of IFNγ signalling

 

Davis Auditorium

Join via SLIDO enter code #WEHIphdcompletion

Including Q&A session

Followed by refreshments in Tapestry Lounge

Suppressor of Cytokine Signalling 1 (SOCS1) is the key negative regulator of responses to interferon (IFN), interleukin (IL)-12 and IL-2 family cytokines, acting in a negative feedback loop to inhibit signalling through direct interaction with the JAK1, JAK2 and TYK2 tyrosine kinases. However, how SOCS1 selectively regulates these cytokine pathways has remained an open question. In addition, although SOCS1 had previously been reported to localise to the nucleus, the impact of SOCS1 nuclear localisation on its ability to inhibit JAK signalling had not been addressed.

Grace’s PhD project investigated how the kinetics and spatial localisation of SOCS1 expression related to its ability to inhibit JAK-STAT signalling. Grace utilised a novel mouse strain that had a Halo tag knocked into the SOCS1 locus, enabling analysis of Halo-SOCS1 expression, subcellular localisation and the SOCS1 interactome. Grace demonstrated that SOCS1 cross-regulation of GM-CSF signalling was dose dependent, and discovered that SOCS1 nuclear localisation occurred via the importin-α, KPNA6. She refined our understanding of the nuclear localisation signal (NLS) in SOCS1 and demonstrated that nuclear localisation of SOCS1 was required for effective inhibition of IFNγ-induced JAK1 activity, revealing a novel aspect of SOCS1 biology.

Ongoing work is evaluating the impact of rare genetic variants in the SOCS1 N-terminal region and NLS, in patients who are susceptible to infectious diseases.

All welcome!