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.
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.
• • •
Missing some Tweet in this thread? You can try to
force a refresh
Hello and welcome to this week’s #DBIOTweetorial by Prof. Madhusudhan Venkadesan @v_madhu. Let’s go!
Feet and fins are quite different in their anatomy. But both have to be stiff enough to withstand the forces of propulsion. Are there deeper connections between them?
All land vertebrates, or tetrapods, evolved from aquatic ancestors over 370 million years ago. So we and all land vertebrates are fish, in a manner of speaking!
Limbs evolved from fins, but the earliest tetrapod probably used a fin to move on land.
Hello, it's a gorgeous Thursday! Time for a #DBIOTweetorial. A special edition this week — an inaugural *Editweetorial* by your host today, Prof. Bill Bialek @wbialek. #DBIOEditweetorial
Biological systems are complicated. If we try to make “realistic” models we are led into a forest of parameters. If we are going to have a theoretical physicist’s understanding of life, we have to find principles that cut through this complexity.
Maybe a #DBIOEditweetorial provides just enough space to summarize different strategies in the search for principles. Links are to papers that illustrate these ideas, and of course are just a sampling. Please respond with your own favorites.
Have you seen images of bacteria and wondered, “How do they form such strange shapes?” or “Why do they all look so different?” Join us for today's #DBIOTweetorial as we dive into how and why bacteria adopt the shapes they do! #EngageDBIO@goleylab@jordanmbarrows
As Kevin Young eloquently put it, “To be brutally honest, few people care that bacteria have different shapes. Which is a shame, because the bacteria seem to care very much.” Check out how diverse bacterial shapes can be! tinyurl.com/6d93vce4tinyurl.com/uvbtwvs3
Bacterial shape is largely determined by the peptidoglycan (PG) cell wall, a large macromolecule that surrounds cells and provides structure and support. PG is necessary to maintain cell shape - cells burst when treated with drugs that target PG! tinyurl.com/m4dys6hb
Are the screaming BroodX cicadas driving you nuts? Wonder how such tiny insects even make such a racket? You’ve come to the right place! I study how insects make and hear sound. By the end of this I hope I can show what biophysical marvels they are! #DBIOTweetorial@NatashaMhatre
So what is sound? It’s a disturbance in a medium, generated by a moving object. In this cool gif, by @drussellpsu, you can you see a grey bar moving back and forth within a pipe. The air in the pipe is pushed around, and the disturbance within it (sound) travels through the air.
So anything that moves makes a sound?
Yup, pretty much! The world is full of it: the wind shakes leaves, they rustle; tires vibrate because of friction, and they rumble.
But how ‘loud’ the sound is depends on quite a few things!
It's #DBIOtweetorial time, with your host @gibbological from @isbsci. Today, you'll get some facts about the ~10^13 microbes that call your gut home. By the end, I hope that you'll see yourself as much more than a mere human. You are an ecosystem! #EngageDBIO#microbiome 💩🦠🧑🔬
In the womb, we are sterile (obgyn.onlinelibrary.wiley.com/doi/abs/10.111…). At birth, our mothers (and surrounding environment) act as our 'sour-dough starter culture,' inoculating us with hundreds-to-thousands of species. The exact composition of this 'microbiome' is as unique to us as our genome.
Topologically speaking, humans are doughnuts. The entire outside of this doughnut is *covered* in microbes (mostly bacteria). Most of our microbes live in the colon. There are about 3*10^13 human cells and 4*10^13 bacterial cells in the body (doi.org/10.1371/journa…).
It's #DBIOtweetorial time! Your host is Saad Bhamla @BhamlaLab. Today we'll learn about 10 ultrafast movements in organisms - from single cells to multicellular beasts. We hope to get you thinking engg+bio+physics of extreme movements. #EngageDBIO#UltrafastOrganisms.
Contrary to common perception, cheetahs and falcons are not the fastest animals. Mantis shrimps for example can use a saddle-shaped spring to hammer at ~100,000 m/s^2. This is so blazing fast, it cavitates surrounding fluid. nature.com/articles/42881…
Trap jaw ants use their spring-loaded jaws to jump at faster acceleration of 10^6 m/s^2 in 0.06 ms. Faster than the blink of an eye or a bullet from a gun !! How to build robots at this scale and speed remains an open challenge. pnas.org/content/103/34…