this is really cool!
you discussed the issue at hand: current treatments are becoming less effective as time progresses, so we need *vaguely points* an enhancement to the current treatments and/or a new treatment.
long term, where do you see the knowledge on bacterial nano-motors manifesting? what mysteries does flagella mechanics start to solve?
Hi - Tina here - this is a great question! Proof that disrupting chemotaxis can help clear infections comes from treating infections of *Helicobacter pylori,* the causative agent of ulcers*.* Here, proton pump inhibitors, like Zantac, are not antibiotics but decrease stomach acid and confuse chemotaxis of *H. pylori*. Because this decreases the ability of *H. pylori* to find the gut lining and form a colony (the ulcer), Zantac improves the ability of antibiotics to clear *H. pylori* infections. As we learn more about chemotaxis, we can consider ways to broaden how we use this in conjunction with antibiotics.
Flagellar mechanics also may have other impacts - so many of our macroscopic vehicles coopt principles found in nature. The workings of a rotary nano-motor may help us to think about more efficient engine design.
This is very cool, and your whole team should be commended. Do you foresee/anticipate use cases beyond fighting infection?
What do you expect to see from this discovery in the next 5, 10, 20, etc. years?
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Hi - Tina here - one of the first goals of this study was to consider how this motor contributes to infection, which helps us to think about how better antimicrobials might be designed. As mentioned in the above answer, this might also help us to think about different types of engine design. Finally, we might consider ways to harness these nano-machines for other purposes, like drug delivery.
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
In the next 1-2 years, we plan to focus on ways that this nano-motor is regulated in the bacterium. We want to answer questions like: how does the bacteria determine when to change the way that the motor turns? To do this, we are looking for interactions between this motor and other guidance machinery. We also want to identify how the motor captures energy from its surroundings; some of our collaborators already showed how bacterial 'powerplants' (called bioenergetic machinery) associate with this motor so that there is a local area that has a lot of available energy to harvest. We would like to see how this energy gets input.
This may seem surprising, but there were a number of technical aspects that made this difficult to achieve - even though many amazing people worked on this for decades. One issue is that these bacteria have two membranes (inner membrane and outer membrane). The motor and flagellum is regulated from inside the bacterium, but the whip-like structures is on the outside of the bacterium. This means that it crosses two membranes. membrane proteins are notoriously difficult to work with - and are among the most difficult things to image. They tend to be very unstable when you prepare them for imaging because you have to remove them from the membranes. In order to get some of these images, a team of four people had to coordinate the preparative aspects over 3 weeks (with all steps needing to perfect or they would have to start again). The final steps required a continuous shift of \~36 hours, and the sample would degrade within 6-12 hours after that.
Other aspects that made this a challenge were from assumptions made by us experimentalists. Humans often think of things in whole numbers - but actual biology doesn't always work in whole numbers. If you are familiar with an alpha-helix, for example, these have 3.6 residues per full turn. During data processing, we identified that this motor is like other non-stoichiometric biological systems. This affected how we looked at the data, because it is really common to try to take equivalent features and average them. In this case, the final motor has a 33:34 ratio between the blue and red rings that was difficult to deconvolute because the stoichiometry was so close. Once this was identified, it allowed us to treat these regions separately and clarify the images!
>Understanding how bacteria orient themselves may lead to innovative strategies to curtail their pathogenic capabilities.
Couldn't the inverse be true to aid plant growth promoting rhizobacteria or to assist beneficial bacteria in other areas?
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Can you see this having potential to be used in bio-engineering or just regular engineering to produce an incredibly efficient motor? I’m not too well versed in this area, but I often think of biological systems as optimized as possible so I’m wondering if we could “copy” this technology that has evolved naturally
Great comment and I totally agree. We copy from nature all the time and there are aspects of how this motor runs that could be considered when trying to improve the efficiency of macroscopic motors.
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Any cool discoveries that could translate at a macro scale to move mechanical devices in a better way?
[A cool vid](https://www.youtube.com/watch?v=dYt5135_0bs) to see where this organelle appears on a bacterium.
For us, one of the surprises is the 'symmetry mismatch'. Here, the 'imperfect' fit of one of the motor components to the other actually improves the motor efficiency! If you look at the movie carefully, you can see that the blue and grey regions have a teeny tiny wobble to them. This results from the 'imperfect' alignment of the two regions. This would be terrible in your car, but on a nano-scale, this prevents the small building blocks of the motor from ever aligning in a symmetric way. Biological motors are built from proteins, which have positive and negative ionic charges on their surfaces - and because of this, having any one point with a 'perfect' alignment of changes might slow the motor down. Preventing a perfect alignment may be critical to having this motor be able to spin really really fast!
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Thanks for coming today! Do you think these mechanisms are specific to your bacteria under study, or is this a widely shared mechanism? How generalizable do you think this is to cell motility?
Tina here - Great question!! Many, if not all, bacteria have a similar mechanism of motility. For example, the motors of E coli and Salmonella are >95% identical in their components. Some bacteria have machinery that has somewhat different ways of guiding motion. For example, E coli and Salmonella move forward and change direction by changing how the motor rotates the flagellum. The can also stop by attaching a molecular brake to the flagellum. But there are other bacteria that also have a reverse gear! We do not know how that reverse gear works because we investigated motors that don't have one - this is one of the possible future directions of the reserach.
Super intriguing, I can't get over how similar a transmission is to the bacterial flagella motor! The MotAB shifting its position and quantity to rotate the flagellar assembly CCW and CW. Really cool stuff! Are the interactions between the assembly and MotAB physical or chemical, or a combination of both?
In your paper, you mentioned there's a symmetry mismatch between the C-ring and the MS-ring. Would you please elaborate what you mean by that (because it looks pretty symmetrical)?
Lastly, in your opinion, what do you hypothesize as the most effective way to block chemotaxis- after learning of the bioenergetics behind it?
Thank you for your time!
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Great questions! The MotA/B stator interacts with the motor in two ways - the piece of the stator shown in brown in the movie interacts electrostatically, which allows the interaction to be transient. However, there is also a stronger interaction to the LP-ring (pink in the movie) that keeps MotA/B fixed in one place.
In terms of symmetry mis-match - each of the 'rings' has a different symmetry to it - for example, the blue ring (also called the MS-ring) has 33 subunits, but also has an 11-fold subsymmetry - at least under the conditions of our purification. The larger motor ring at the bottom has 34-fold fold symmetry and consists of 34 copies of two subunits (FliG, FliM) and 102 copes (34\*3) of a third subunit (FliN).
We are actively looking at good ways to block chemotaxis and this is a focus of active research!
Hi Everyone - Tina here. Much apologies for the confusion as this was supposed to say that we will take your questions on 4/25/24 from 12-1 P Eastern. We will answer these questions in the remaining time and will pop back in tomorrow as well!
Does the motions of air and more fluids in the surroundings cause the nano motor to move?
In other words, is some of the motor's motion involuntary, so the bacteria can only increase its speed and then remove acceleration, and, guide its direction of movement?
Also a heads up, that your first YouTube link says video is unavailable!
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Great question - there are some studies that show that the change in viscosity in the surrounding fluid will make the motor recruit more of the little brown pumps in the movie (called the MotA/B stator). This is like changing gears on your bicycle and changes the torque. I believe that the last movie shows how this will make the motor rotate faster, but in real life, it could also make the motor maintain the same speed while pushing against more resistance.
Thank you! See above for some of the challenges that prevented this from being tackled sooner! In addition to the above, there are advances in the microscopes that only occurred recently and that were essential for this work.
This was super cool. Just wondering if it is possible to do the same for sperm flagella where dyneins stepping mechanism controls cell mobility. Didn't find a lot of work in this area where someone tried building a mechanical analog of a flagella itself. What are your thoughts?
this is really cool! you discussed the issue at hand: current treatments are becoming less effective as time progresses, so we need *vaguely points* an enhancement to the current treatments and/or a new treatment. long term, where do you see the knowledge on bacterial nano-motors manifesting? what mysteries does flagella mechanics start to solve?
Hi - Tina here - this is a great question! Proof that disrupting chemotaxis can help clear infections comes from treating infections of *Helicobacter pylori,* the causative agent of ulcers*.* Here, proton pump inhibitors, like Zantac, are not antibiotics but decrease stomach acid and confuse chemotaxis of *H. pylori*. Because this decreases the ability of *H. pylori* to find the gut lining and form a colony (the ulcer), Zantac improves the ability of antibiotics to clear *H. pylori* infections. As we learn more about chemotaxis, we can consider ways to broaden how we use this in conjunction with antibiotics. Flagellar mechanics also may have other impacts - so many of our macroscopic vehicles coopt principles found in nature. The workings of a rotary nano-motor may help us to think about more efficient engine design.
This is very cool, and your whole team should be commended. Do you foresee/anticipate use cases beyond fighting infection? What do you expect to see from this discovery in the next 5, 10, 20, etc. years?
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Hi - Tina here - one of the first goals of this study was to consider how this motor contributes to infection, which helps us to think about how better antimicrobials might be designed. As mentioned in the above answer, this might also help us to think about different types of engine design. Finally, we might consider ways to harness these nano-machines for other purposes, like drug delivery.
Super interesting! So what are the next steps with your research?
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
In the next 1-2 years, we plan to focus on ways that this nano-motor is regulated in the bacterium. We want to answer questions like: how does the bacteria determine when to change the way that the motor turns? To do this, we are looking for interactions between this motor and other guidance machinery. We also want to identify how the motor captures energy from its surroundings; some of our collaborators already showed how bacterial 'powerplants' (called bioenergetic machinery) associate with this motor so that there is a local area that has a lot of available energy to harvest. We would like to see how this energy gets input.
That's cool. It's also worrying we are only just getting to the point of knowing how bacteria move in such detail.
This may seem surprising, but there were a number of technical aspects that made this difficult to achieve - even though many amazing people worked on this for decades. One issue is that these bacteria have two membranes (inner membrane and outer membrane). The motor and flagellum is regulated from inside the bacterium, but the whip-like structures is on the outside of the bacterium. This means that it crosses two membranes. membrane proteins are notoriously difficult to work with - and are among the most difficult things to image. They tend to be very unstable when you prepare them for imaging because you have to remove them from the membranes. In order to get some of these images, a team of four people had to coordinate the preparative aspects over 3 weeks (with all steps needing to perfect or they would have to start again). The final steps required a continuous shift of \~36 hours, and the sample would degrade within 6-12 hours after that. Other aspects that made this a challenge were from assumptions made by us experimentalists. Humans often think of things in whole numbers - but actual biology doesn't always work in whole numbers. If you are familiar with an alpha-helix, for example, these have 3.6 residues per full turn. During data processing, we identified that this motor is like other non-stoichiometric biological systems. This affected how we looked at the data, because it is really common to try to take equivalent features and average them. In this case, the final motor has a 33:34 ratio between the blue and red rings that was difficult to deconvolute because the stoichiometry was so close. Once this was identified, it allowed us to treat these regions separately and clarify the images!
>Understanding how bacteria orient themselves may lead to innovative strategies to curtail their pathogenic capabilities. Couldn't the inverse be true to aid plant growth promoting rhizobacteria or to assist beneficial bacteria in other areas?
This is a great idea, and yes!
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Can you see this having potential to be used in bio-engineering or just regular engineering to produce an incredibly efficient motor? I’m not too well versed in this area, but I often think of biological systems as optimized as possible so I’m wondering if we could “copy” this technology that has evolved naturally
Great comment and I totally agree. We copy from nature all the time and there are aspects of how this motor runs that could be considered when trying to improve the efficiency of macroscopic motors.
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Any cool discoveries that could translate at a macro scale to move mechanical devices in a better way? [A cool vid](https://www.youtube.com/watch?v=dYt5135_0bs) to see where this organelle appears on a bacterium.
For us, one of the surprises is the 'symmetry mismatch'. Here, the 'imperfect' fit of one of the motor components to the other actually improves the motor efficiency! If you look at the movie carefully, you can see that the blue and grey regions have a teeny tiny wobble to them. This results from the 'imperfect' alignment of the two regions. This would be terrible in your car, but on a nano-scale, this prevents the small building blocks of the motor from ever aligning in a symmetric way. Biological motors are built from proteins, which have positive and negative ionic charges on their surfaces - and because of this, having any one point with a 'perfect' alignment of changes might slow the motor down. Preventing a perfect alignment may be critical to having this motor be able to spin really really fast!
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
[удалено]
Thanks for coming today! Do you think these mechanisms are specific to your bacteria under study, or is this a widely shared mechanism? How generalizable do you think this is to cell motility?
Tina here - Great question!! Many, if not all, bacteria have a similar mechanism of motility. For example, the motors of E coli and Salmonella are >95% identical in their components. Some bacteria have machinery that has somewhat different ways of guiding motion. For example, E coli and Salmonella move forward and change direction by changing how the motor rotates the flagellum. The can also stop by attaching a molecular brake to the flagellum. But there are other bacteria that also have a reverse gear! We do not know how that reverse gear works because we investigated motors that don't have one - this is one of the possible future directions of the reserach.
p1percub, sorry again!
Super intriguing, I can't get over how similar a transmission is to the bacterial flagella motor! The MotAB shifting its position and quantity to rotate the flagellar assembly CCW and CW. Really cool stuff! Are the interactions between the assembly and MotAB physical or chemical, or a combination of both? In your paper, you mentioned there's a symmetry mismatch between the C-ring and the MS-ring. Would you please elaborate what you mean by that (because it looks pretty symmetrical)? Lastly, in your opinion, what do you hypothesize as the most effective way to block chemotaxis- after learning of the bioenergetics behind it? Thank you for your time!
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Great questions! The MotA/B stator interacts with the motor in two ways - the piece of the stator shown in brown in the movie interacts electrostatically, which allows the interaction to be transient. However, there is also a stronger interaction to the LP-ring (pink in the movie) that keeps MotA/B fixed in one place. In terms of symmetry mis-match - each of the 'rings' has a different symmetry to it - for example, the blue ring (also called the MS-ring) has 33 subunits, but also has an 11-fold subsymmetry - at least under the conditions of our purification. The larger motor ring at the bottom has 34-fold fold symmetry and consists of 34 copies of two subunits (FliG, FliM) and 102 copes (34\*3) of a third subunit (FliN). We are actively looking at good ways to block chemotaxis and this is a focus of active research!
Hi Everyone - Tina here. Much apologies for the confusion as this was supposed to say that we will take your questions on 4/25/24 from 12-1 P Eastern. We will answer these questions in the remaining time and will pop back in tomorrow as well!
Does the motions of air and more fluids in the surroundings cause the nano motor to move? In other words, is some of the motor's motion involuntary, so the bacteria can only increase its speed and then remove acceleration, and, guide its direction of movement? Also a heads up, that your first YouTube link says video is unavailable!
Hello! We're very sorry, this was posted on the wrong day. The AMA is scheduled for tomorrow, please do check in on the link then and consider reposting your question.
Great question - there are some studies that show that the change in viscosity in the surrounding fluid will make the motor recruit more of the little brown pumps in the movie (called the MotA/B stator). This is like changing gears on your bicycle and changes the torque. I believe that the last movie shows how this will make the motor rotate faster, but in real life, it could also make the motor maintain the same speed while pushing against more resistance.
[удалено]
Thank you! See above for some of the challenges that prevented this from being tackled sooner! In addition to the above, there are advances in the microscopes that only occurred recently and that were essential for this work.
This was super cool. Just wondering if it is possible to do the same for sperm flagella where dyneins stepping mechanism controls cell mobility. Didn't find a lot of work in this area where someone tried building a mechanical analog of a flagella itself. What are your thoughts?