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New Proteomic Study of Trypanosome Cell Cycle
A new study entitled “Proteomic Analysis of the Cell Cycle of Procylic Form Trypanosoma brucei” has just been published in Molecular and Cellular Proteomics (Crozier et al., 2018, Mol Cell Proteomics 2018 17: 1184-1195). This study resulted from a collaboration between the laboratories of Mike Ferguson (BCDD) and Angus Lamond (GRE). Trypanosoma brucei is an evolutionarily divergent eukaryotic protozoan parasite that causes human and animal trypanosomiasis (also called ‘sleeping sickness’) in sub-Saharan Africa. In this study, the authors developed a single-step centrifugal elutriation method, allowing the isolation of synchronous Gap1 (G1)-phase procyclic trypanosomes at a large enough scale for a detailed proteomic analysis of the cell cycle. Using ten-plex tandem mass tag (TMT) labeling and mass spectrometry (MS)-based proteomics, over 5,300 trypanosome proteins were identified and their expression quantified across the cell cycle. The expression of 384 proteins was shown to vary significantly during cell cycle progression and this included 40 novel cell cycle regulated proteins that are essential for trypanosome survival. Many of the novel cell cycle regulated proteins identified were independently confirmed to show cell cycle regulation by reference to the microscopy-based ‘Tryp-Tag’ database. As the 40 essential proteins found to be cell cycle regulated are classed as hypothetical proteins of unknown function, lacking obvious sequence homology to proteins characterized in other eukaryotes, they include some promising new candidates to target with drugs for treating sleeping sickness, because they could selectively interfere with trypanosomatid, rather than host, cell division. All of these new data on cell cycle regulated proteins in Trypanosoma brucei have been made conveniently available to the community in a searchable online database.
Research in the Lamond Lab that has created powerful new software tools for management, visualisation and analysis of proteomics big data has led to the formation of a new Univeristy of Dundee Spin out company called Platinum InformaticsPlatinum informatics has been awarded a SMART:SCOTLAND feasibility grant from Scottish Enterprise. The award will allow the development of a 'Processing Pipeline', a cloud-based 'Big Data' processing and analysis tool. This will further expand their suite of software for advanced data management. Platinum have also made the Converge Challenge Top 30. Converge Challenge is the leading, pan Scotland, company creation programme for staff, students and recent graduates of Scottish Universities and Research Institutes with the aim of creating a new generation of entrepreneurs in Scotland. We wish them every success in this entrepreneurial endeavour.
Members of the Lamond Lab (Tony Ly, Aki Endo, Alejandro Brenes, Vackar Afzal, Andrea Pawellek and Angus Lamond) have generated one of the most comprehensive analyses of the changes in the regulation and turnover of proteins in response to Src activation of cancer transformation published in Wellcome Open Research Proteome-wide analysis of protein abundance and turnover remodelling during oncogenic transformation of human breast epithelial cells. The signature of Src-responsive proteins is highly predictive of poor patient survival across multiple cancer types.
‘Volcano’ plots of –log10 p-value versus log2 fold change for the seven time points of Src activation, and cancer transformation.
Not only are these data available through the Wellcome Open Research portal but also through The Encyclopedia of Proteome Dynamics where you can investigate the effects of Src transformation on your proteins of interest.
This paper has now passed peer review and will shortly be available on Pubmed, and the revised version of the manuscript on Wellcome Open Research.
A collaboration with Professor Fiona Watt at Kings College London (Centre for Stem Cells & Regenerative Medicine), Tony Ly, Haru Yoshikawa, and Angus Lamond has shown the effect of stalled ribosomes on the homeostasis of the epidermis, An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis published in Nature.
"Different mRNA features can lead to ribosome stalling during translation elongation. Because the accumulation of stalled ribosomes on mRNAs is toxic, cells have evolved mechanisms to rescue and recycle stalled ribosomes by inducing their release and the degradation of the associated nascent polypeptides." A protein responsible for this rescue mechanism, Pelota (Pelo), when knocked out, resulted in loss of effective skin barrier function, scaly skin and epidermal thickening.