A spatially-resolved human cell model and its application to RNA processing
Spatial organization is a fundamental characteristic of cells, achieved by utilizing both membrane-bound and non-bound organelles
In this talk Dr. Zhaleh Ghaemi will describe how we constructed a spatially resolved human whole-cell (HeLa) model from experiment-based structural, morphological and reaction network data to describe the mRNA splicing process (the process that readies RNA transcripts for translation) and dynamics of splicing particles. We then performed stochastic simulations for up to 15 minutes of biological time of the entire cell.
We find that even a slight increase of splicing particle localization in nuclear speckles (non-membrane-bound organelles) leads to a disproportionate enhancement of mRNA splicing and reduction in the transcript noise; and that compartmentalization is critical for the yield of correctly assembled splicing particles. Our model also predicts that the distance between genes and speckles has a considerable effect on the mRNA production rate, further emphasizing the importance of genome organization around speckles. The HeLa cell model, including organelles and subcompartments, provides an adaptable foundation to study many cellular processes which are strongly modulated by spatio-temporal heterogeneity
About the speaker
Ryszard Auksztulewicz conducts empirical and theoretical work at the interface of cognitive, computational, and systems neuroscience, focusing primarily on the neural mechanisms of predictive coding and their modulation by cognitive factors. He is currently funded by the European Commission’s Marie Skłodowska-Curie Global Fellowship for his work on neural mechanisms of prediction signalling, and is hosted by the Neuroscience Department of the MPI for Empirical Aesthetics, Frankfurt am Main (working closely with Prof. Lucia Melloni and Prof. David Poeppel), and the Department of Neuroscience, City University of Hong Kong (Prof. Jan Schnupp). Previously, Ryszard has worked in the world’s leading cognitive and computational neuroscience groups at University College London (Prof. Karl Friston) and Oxford University (Prof. Kia Nobre), spearheading empirical and modelling studies of the neural mechanisms of prediction error signalling. Most of his previous and ongoing work is directly related to predictive coding and auditory mismatch signalling in the brain.