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The endosomal network comprises a series of interconnected membrane bound compartments that in regulating the sorting and signaling of proteinaceous cargoes including receptors, transporters and adhesion molecules, orchestrates and fine-tunes numerous cellular processes. A major challenge is to achieve a thorough molecular description of how this network operates, and in so doing, how defects contribute to the pathoetiology of human disease.
To date our understanding of endosomal sorting has been restricted by a tendency to focus on individual ‘model’ cargoes, and the ‘isolated’ characterization of protein complexes that define individual sorting events. To achieve a thorough understanding we must break new ground and take a global view of cargo proteins and an integrated approach to how the mechanistic complexities of multiple sorting complexes are orchestrated, not only in individual cultured cells but also within the in vivo context of tissues and physiological systems.
In the laboratory we seek to address these issues by combining new experimental protocols utilizing the power of quantitative proteomics to identify sorting complexes and achieve an unbiased global analysis of the cargoes that they sort. In combining these molecular approaches with in vivo studies in model organisms and collaborative genetic analysis of patient cohorts, our research aims to define the underlying defects in endosomal sorting and signaling that occur in human disease.
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1/01/21 → 31/12/25
McMillan, K. J., Banks, P. J., Hellel, F. L., Carmichael, R. E., Clairfeuille, T., Evans, A. J., Heesom, K. J., Lewis, P., Collins, B. M., Bashir, Z. I., Henley, J. M., Wilkinson, K. A. & Cullen, P. J., 12 Jul 2021, In: eLife. 10, 32 p., e59432.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile12 Downloads (Pure)
Acute inactivation of retromer and ESCPE-1 leads to time-resolved defects in endosomal cargo sortingEvans, A. J., Daly, J., Anuar, A. N. K., Simonetti, B. & Cullen, P. J., 3 Aug 2020, In: Journal of Cell Science. 133, jcs246033.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile35 Downloads (Pure)
A heterodimeric SNX4:SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assemblyAnton, Z., Betin, V. M. S., Simonetti, B., Traer, C. J., Attar, N., Cullen, P. J. & Lane, J. D., 15 Jul 2020, In: Journal of Cell Science. 133, 14, 38 p., jcs246306.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile30 Downloads (Pure)