Bacterial-induced partial host cell reprogramming figure
More detail about the bacterial-induced partial host cell reprogramming figure
Scientists in the Rambukkana laboratory pioneered the fusion of infection biology and regeneration biology themes by linking partial cellular reprogramming and tissue regeneration and organ growth to bacterial infections. Findings observed by scientists (in a cartoon) identified key events in bacterial-induced host cell reprogramming; images from clockwise: mitotic stage of cell division cycle (green) in the presence of bacteria (red); transcriptional changes in the nuclei (purple) in the presence of bacteria (green), re-differentiation of bacterially reprogrammed stem cells (green) into injured muscle (red), and recruiting innate immune cells (blue) by reprogrammed/stem cells (green). Our goal is to translate these natural bacterial strategies to new kind of drug development that could activate endogenous repair pathways promoting regeneration of diseased tissues and rejuvenation of aging tissues/organs, potentially halting or preventing cancer development and increase the healthy lifespan.
Progenitor/Stem cell-like cells (green) generated from reprogramming of adult Schwann cells by bacterial infection fuse with and re-differentiate into skeletal muscles (a striated muscle fibre in red). The finding published in Cell (Masaki et al) has been selected to ‘Best of Cell 2013’ collection in 2014 by the journal Cell, Top).
Translating bacterial ingenuity of organ growth for developing safer therapeutic regeneration and rejuvenation strategies: lessons from long-lived and larger mammalian model nine-banded armadillos. The only mammal in the animal kingdom that produces four genetically identical/clonal litters, nine-banded armadillos, is also a natural animal host for Mycobacterium leprae, which propagate in the animal liver. The study shows that bacteria effectively hijack yet unknown endogenous regenerative or rejuvenating pathways to proliferate and partially reprogram and re-differentiate adult hepatocytes in vivo contributing to the growth and rejuvenation of liver mass as a functionally and architecturally intact organ with a proportionate expansion of vascular and bile ductal systems without causing injury, fibrosis or tumorigenesis.
The background image shows machine learning of classified liver cells in situ; classical hepatocyte nuclei (yellow) binucleated nuclei (orange) in hepatic plates and other liver cells (purple) from an infected armadillo liver. In left show four clonal siblings and histological and molecular features of infected armadillo livers, which are very similar to normal human adult livers (right). Our current studies are directed to harnessing mechanistic that bacteria co-evolved to grow the entire liver organ in living animals without cancer formation. We anticipate such pre-clinical approach to repair or rejuvenate the diseased or aging livers could be translatable to humans in future.