SUMO

The many faces of the Small Ubiquitin like Modifier

Current: Subhradip Das, Amrita Roy

Past: Amar Soory, Bhagyashree Kaduskar, Mithila Handu, Prajna Nayak, Sushmitha Hegde

The post-translational modifier, SUMO, can modulate the structure, folding, stability, dynamics, function or location of a target protein post conjugation. Many proteins that are SUMO targets play important roles in important physiological processes. We have chosen immune signaling and early embryonic development as two stages to understand SUMO's ability to modulate biological phenomenon. In the Immune system, using quantitative proteomics, we have defined a set of proteins that change their SUMOylation status after mock infection (Handu et. al., 2015). Many of these SUMO-conjugated proteins have important roles in immune signaling and we are currently working towards defining the effect of SUMO conjugation on each of the central immune signaling pathways, Toll/NfkB, IMD/NFkB and the JNK signal transduction cascades. Proteomics has also been used to define a set of proteins SUMO conjugated in the early 0-3 embryo by the Courey laboratory (Nie et. al., 2009), where the primary axis (Anterior/Posterior; Dorsal/Ventral; Terminal), of the animal are being established. We are using CRISPR/Cas9 based genome editing to generate SUMO-conjugation resistant proteins and studying their effect in the organism.

SUMO conjugation regulates the Innate Immune Response

We are attempting to understand roles for the post-translational modifier SUMO in regulating the fly immune response, with a focus on immune signaling. Our methodology incorporates the identification of proteins that are SUMO conjugated proteins in response to infection and using Proteomics and then generating non-SUMOylatable variants of these 'target' proteins using CRISPR/Cas9 genome editing. The shaded proteins in the NFkB signaling cascades (Figure) include our current targets.

SUMO conjugation regulates immune signalling. Hegde S, Soory A, Kaduskar B, Ratnaparkhi GS. Fly (Austin). 2020 Mar-Dec;14(1-4):62-79. doi: 10.1080/19336934.2020.1808402.

Caspar SUMOylation regulates Drosophila lifespan. Kaduskar B, Trivedi D, Ratnaparkhi GS. MicroPubl Biol. 2020 Aug 2;2020:10.17912/micropub.biology.000288.

SUMO conjugation in early embryonic development

Early embryonic development (0-3 hour, post fertilization), in the fruit fly, is driven by maternal factors, including proteins that are post-translationally modified by SUMO. Since reduction of maternal SUMO leads to A/P & D/V patterning defects, we are curious to understand mechanistic roles played by SUMO conjugation in this critical, foundation-laying stage of animal development. Figure shows the major Gene Networks and the master regulatory protein in the network.