Mapping diversity in African trypanosomes using high resolution spatial proteomics

Abstract

African trypanosomes are dixenous eukaryotic parasites that impose a significant human and veterinary disease burden on sub-Saharan Africa. Diversity between species and life-cycle stages is concomitant with distinct host and tissue tropisms within this group. Here, the spatial proteomes of two African trypanosome species, Trypanosoma brucei and Trypanosoma congolense, are mapped across two life-stages. The four resulting datasets provide evidence of expression of approximately 5500 proteins per cell-type. Over 2500 proteins per cell-type are classified to specific subcellular compartments, providing four comprehensive spatial proteomes. Comparative analysis reveals key routes of parasitic adaptation to different biological niches and provides insight into the molecular basis for diversity within and between these pathogen species.

Differentiation granules, a dynamic regulator of T. brucei development

“…We then grouped the proximal proteins according to their localisation in bloodstream forms as identified by ref. 36 . (Supplementary Fig.…”

Characterization of novel and essential kinetoplast-associated proteins inTrypanosoma brucei

“…From the recent Hyper-LOPIT spatial resolution of T. brucei (Moloney et al, 2023), our novel kinetoplast proteins are listed simply as constituents of the mitochondrial matrix. While this study achieved excellent resolution of mitochondrial compartments and complexes, including a subfraction of the matrix, enriched in ribosomal subunits, the kinetoplast was not resolved in a similar manner.…”

Recent Advancements in Subcellular Proteomics: Growing Impact of Organellar Protein Niches on the Understanding of Cell Biology

“…Subcellular proteomics has emerged as a rapidly growing field, with many publications shedding light on subcellularly resolved protein information from subcellular compartments to single cells. ,,,, From a technology development perspective, it is a highly interdisciplinary field that integrates imaging and image analysis, subcellular analyses, mass spectrometry, and computational machine learning methods. Published global subcellular proteomic approaches focused more on static cellular maps , rather than information on protein dynamics. ,, Subcellular proteomics employs multiple translational techniques to study cellular protein dynamics, protein–protein interaction, and protein relocalization following perturbations. Besides the numerous advantages, subcellular proteomics studies post specific technical and conceptual challenges for method developers.…”

“…4,62,63,81,82 subcellular proteomic approaches focused more on static cellular maps 56,60 rather than information on protein dynamics. 21,22,31 Subcellular proteomics employs multiple translational techniques to study cellular protein dynamics, protein−protein interaction, and protein relocalization following perturbations. Besides the numerous advantages, subcellular proteomics studies post specific technical and conceptual challenges for method developers.…”

“…Recent technological advancements in high-throughput quantitative mass spectrometry, , imaging-based microscopy, interactome mapping, and computational machine-learning methods for data analysis have revolutionized how we investigate organellar protein functions. The synergistic subcellular proteomic approaches and refined experimental techniques have enabled significant progress in understanding and quantifying subcellular protein domains at single-cell levels, intact tissue specimens, , and even at subcellular phospho-proteome levels. , …”