Dataset Information

Building spectral libraries to analyze phosphopeptides in colorectal cancer organoids

ABSTRACT: The goal of this project was to build SWATH Spectral libraries to analyze phosphopeptides from colorectal cancer organoids.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Peter Blattmann

LAB HEAD: Ruedi Aebersold

PROVIDER: PXD018862 | Pride | 2023-12-10

REPOSITORIES: Pride

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Publications

Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer.

Plattner Christina C Lamberti Giorgia G Blattmann Peter P Kirchmair Alexander A Rieder Dietmar D Loncova Zuzana Z Sturm Gregor G Scheidl Stefan S Ijsselsteijn Marieke M Fotakis Georgios G Noureen Asma A Lisandrelli Rebecca R Böck Nina N Nemati Niloofar N Krogsdam Anne A Daum Sophia S Finotello Francesca F Somarakis Antonios A Schäfer Alexander A Wilflingseder Doris D Gonzalez Acera Miguel M Öfner Dietmar D Huber Lukas A LA Clevers Hans H Becker Christoph C Farin Henner F HF Greten Florian R FR Aebersold Ruedi R de Miranda Noel F C C NFCC Trajanoski Zlatko Z

iScience 20231104 12

Precision oncology approaches for patients with colorectal cancer (CRC) continue to lag behind other solid cancers. Functional precision oncology-a strategy that is based on perturbing primary tumor cells from cancer patients-could provide a road forward to personalize treatment. We extend this paradigm to measuring proteome activity landscapes by acquiring quantitative phosphoproteomic data from patient-derived organoids (PDOs). We show that kinase inhibitors induce inhibitor- and patient-speci ...[more]

PMID: 38047086

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Project description:Many biological processes involve the mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Thus, the challenge of deciphering mTORC1-mediated functions during normal and pathological states in the central nervous system is steep. Because mTORC1 is at the core of translation, we have investigated mTORC1 function in global and regional protein expression. Activation of mTORC1 has been generally regarded to promote translation. Few but recent works have demonstrated that suppression of mTORC1 can promote local protein synthesis. Moreover, excessive mTORC1 activation during disease states represses basal and activity-induced protein synthesis. To determine the role of mTORC1 activation in protein expression, we have used an unbiased, large scale proteomic approach. We provide evidence that a brief repression of mTORC1 activity in vivo by rapamycin has little affect globally, yet leads to a significant remodeling of synaptic proteins, in particular those proteins that reside in the postsynaptic density (PSD). We have also found that curtailing the activity of mTORC1 bidirectionally alters the expression of proteins associated with epilepsy, Alzheimer’s disease, and autism spectrum disorder (ASD)—neurological disorders that exhibit elevated mTORC1 activity. Through a protein-protein interaction network analysis, we have identified common proteins shared among these mTOR-related diseases. One such protein is Parkinson protein 7 (PARK7) which has been implicated in Parkinson’s disease, yet not associated with epilepsy, AD, or ASD. To verify our finding, we provide evidence that the protein expression of PARK7, including new protein synthesis, is sensitive to mTORC1 inhibition. Using cultured neurons from a mouse model of tuberous sclerosis complex (TSC), a disease that displays both epilepsy and ASD phenotypes and has overactive mTOR signaling, we show that PARK7 protein is elevated in the dendrites. Our work offers a comprehensive view of mTORC1 and its role in regulating regional protein expression in normal and diseased states.

Project description:Fomitiporia mediterranea (Fmed) is one of the main fungal species found in grapevine wood rot, also called “amadou”, one of the most typical symptoms of grapevine trunk disease Esca. This fungus is functionally classified as a white-rot, able to degrade all wood structure polymers, i.e., hemicelluloses, cellulose, and the most recalcitrant component, lignin. Specific enzymes are secreted by the fungus to degrade those components, namely carbohydrate active enzymes for hemicelluloses and cellulose, which can be highly specific for given polysaccharide, and peroxidases, which enable white-rot to degrade lignin, with specificities relating to lignin composition as well. Furthermore, besides polymers, a highly diverse set of metabolites often associated with antifungal activities is found in wood, this set differing among the various wood species. Wood decayers possess the ability to detoxify these specific extractives and this ability could reflect the adaptation of these fungi to their specific environment. The aim of this study is to better understand the molecular mechanisms used by Fmed to degrade wood structure, and in particular its potential adaptation to grapevine wood. To do so, Fmed was cultivated on sawdust from different origins: grapevine, beech, and spruce. Carbon mineralization rate, mass loss, wood structure polymers contents, targeted metabolites and secreted proteins were measured. We used the well-known white-rot model Trametes versicolor for comparison. Whereas no significant degradation was observed with spruce, a higher mass loss was measured on Fmed grapevine culture compared to beech culture. Moreover, on both substrates, a simultaneous degradation pattern and the degradation of wood extractives were demonstrated, and proteomic analyses identified a relative overproduction of oxidoreductases involved in lignin and extractive degradation on grapevine cultures, and only few differences in carbohydrate active enzymes. These results could explain at least partially the adaptation of Fmed to grapevine wood structural composition compared to other wood species and suggest that other biotic and abiotic factors should be considered to fully understand the potential adaptation of Fmed to its ecological niche.

Dataset Information

Building spectral libraries to analyze phosphopeptides in colorectal cancer organoids

Publications

Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer.

Similar Datasets

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