Engineering synthetic organelles and their communication networks to control cell fates

The fate and function of mammalian cells are governed by complex intracellular signaling pathways that link surface signals to genetic networks within the nucleus, ultimately regulating gene expression. Transcription factors are proteins that mediate these pathways by binding to specific DNA sequences and activating selected genes. The effects of transcription factors can be rapid and transient enabling cells to adapt to changing conditions by altering cellular functions and guiding cell fate decisions. To leverage this process for controlling cell fate, we sought to create novel intracellular control systems inspired by evolutionary principles. Mitochondria, which originated from free-living bacteria over two billion years ago, are now essential organelles in mammalian cells that are responsible for energy production. We hypothesized that by using extant bacteria as chassis organisms, we could engineer synthetic organelles that mimic mitochondria and function as intracellular “remote control modules” to direct cellular fates and functions. These synthetic organelles are designed to receive signals ​​​from outside the cell – and even from outside the body – and transduce them into transcription factors that modulate gene expression and control cell fates. To achieve this, we developed interkingdom communication pathways that bridge bacterial and mammalian biology, integrating bacterial systems into the host’s intracellular signaling networks. Mitochondria, once free-living bacteria, have since undergone significant genome reduction, retaining only 37 genes, with the majority of mitochondrial proteins encoded by the host genome. In our approach, we have used various bacteria as chassis organisms, gradually removing unnecessary functions and enhancing interdependence between bacterial and mammalian systems. Additionally, we’ve designed genetic reporters – biological “indicator lights” – that can be used to visually track gene regulation, aiding the development of effective synthetic organelles. This innovative approach offers precise spatiotemporal control over cellular reprogramming and differentiation. Ultimately, this technology could enable the targeted regeneration of tissues or organs, offering a revolutionary method for disease treatment through remote manipulation of cells for tissue or organ restoration. Speakers: Christopher Contag Founding Director, Institute for Health Science and Engineering, Inaugural chair, Michigan State University & Stanford University School of Medicine, USA Moderators: Ian F. Akyildiz ITU J-FET Editor-in-Chief and Truva Inc., USA​​​ Wisdom corner Moderators: Alessia Magliarditi ITU Journal Manager, International Telecommunication Union (ITU) AI for Good is identifying innovative AI applications, building skills and standards, and advancing partnerships to solve global challenges. AI for Good is organized by ITU in partnership with over 40 UN Sister Agencies and co-convened with the Government of Switzerland. Join the Neural Network! 👉https://aiforgood.itu.int/neural-netw... The AI for Good networking community platform powered by AI. Designed to help users build connections with innovators and experts, link innovative ideas with social impact opportunities, and bring the community together to advance the SDGs using AI. 🔴 Watch the latest #AIforGood videos!    / aiforgood   📩 Stay updated and join our weekly AI for Good newsletter: http://eepurl.com/gI2kJ5 🗞Check out the latest AI for Good news: https://aiforgood.itu.int/newsroom/ 📱Explore the AI for Good blog: https://aiforgood.itu.int/ai-for-good... 🌎 Connect on our social media: Website: https://aiforgood.itu.int/ X:   / aiforgood   LinkedIn Page:   / 26511907   LinkedIn Group:   / 8567748   Instagram:   / aiforgood   Facebook:   / aiforgood   Disclaimer: The views and opinions expressed are those of the panelists and do not reflect the official policy of the ITU.