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1 Apr, 11 tweets, 5 min read
It's Thursday and time for a #DBIOtweetorial commissioned by the awesome folks at #engageDBIO!
Like a city, inside of the cell is organised by highways and roads (microtubules, actin), motors (dynein, kinesins, myosins) cargoes (e.g. receptors in endosomes, viruses) post-offices sorting cargoes (sorting endosomes), garbage clean-up (autophagosomes, lysosomes) and much more
Every piece of the puzzle listed above is a field on its own! We now know about the exquisite dynamics of microtubules, or how motors move. We know about the process of endocytosis at the plasma membrane and proteins that define distinct endosomal populations (Rabs)
At the level of single cells, how individual processes building up the endosomal network integrate to evince trafficking and signalling outcomes is an exciting field. Individual processes building up the endosomal network are inherently stochastic, making measurements non-trivial
How can we study such processes? Advent of light-sheet based approaches allow imaging of the whole cell volumes with high-temporal resolution. When acquired at high-temporal resolution for long time durations, fast stochastic processes that build up this system can be captured
With whole-cell volumes captured, one can extract quantitative parameters for ALL events, something that was not possible earlier because events would be missed owing to poor time resolution or lack of photo gentleness, that is required for long measurements for sufficient events
Two examples of such an approach applied to endosomes are: measuring the kinetics of phosphoinositide conversion in endosomal populations (He et al. , 2017) and ligand induced whole cell level perturbation and engagement of an early endosomal adaptor (York et al., 2021)
Open questions include mechanisms of endosomal maturations, how the timing of the 'conveyor belt' of endosomes are maintained at a population level. Phosphatases and kinases are at the centre of this (see below and compare the reconstituted system from the Groves lab to this)
Experimental approaches in this field need mathematical biology too. Here are two examples of awesome papers that discuss endosomal maturations and sorting of cargoes. Large numbers of events at whole-cell levels can now be measured to provide experimentally measured parameters. https://pubmed.ncbi.nlm.nih.gov/29490254/ https://pubmed.ncb
Phosphoinositide conversions, by various phosphatases and kinases are at the centre of endosomal conversions. Reconstitution approaches are a powerful way to understanding the mechanisms, for e.g. this stochastic geometry sensing in a kinase-phosphatase competitive reaction
Lastly, understanding the endosomal system beyond proteins that 'regulate' a process in this system is perhaps within reach by developments in imaging, not to mention the importance of every aspect of endosomal trafficking relatable to many diseases, including viral infections. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1315364/ https:

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More from @ApsDbio

25 Mar
It's a beautiful thursday! time for a #DBIOtweetorial commissioned by the awesome folks at #engageDBIO!
First up: “this feather star has too many arms and is too heavy to swim – instead it creeps along the seafloor”

How goes this amazing creature coordinate so many appendages? what kind of physics does it encounter?
When discussing limb coordination, it's probably easier to define what we mean by coordination than 'limb'...
doi.org/10.1038/44416

You might recognise this famous image of '#synchronization', referred to by Huygens as 'an odd kind of sympathy' (1665)

jstor.org/stable/4027017…
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