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What is something you are most proud of?

It appears that the U.S. CIA has been making contributions to universities for the study of extremophiles. Do you know wgat the use-case would be for them? They are at such depths and pressures that they might be a stepping stone organusm to study. If ghey could be coaxed to work in a more moderate context , then they might be able to assist in processing magnesium, iron, or rare earth minerals.

How do you envision to implement this in vivo? There will be innumerable additional challenges (navigating 3D space, tissues etc.) How do you plan to reach tissues? A delivery by the bloodstream would cause heavy immun reactions.

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Are there military applications of this research?

Birgül here again!

A huge THANK YOU to everyone for the great questions! I enjoyed so much answering them! I tried to answer as much as I could, but I couldn't get them all. If you want you can follow me on Twitter for further questions: https://twitter.com/akolpoglu

Cheers,

/birgül

Thanks for the response! Interesting review article.

It does seem like a lot of these studies focus on either in-depth engineering of the bacteria (Like Tal Danino's lab) or lots of post-growth chemical/physical modification. It seems like there might be an opportunity to combine those approaches.

Hi ! Can the biohybrid pass their modifications to other bacteria ? Have they any effect on the human microbiata ? And finally, do you plan to apply this king of technology to the animals (for exemple cows or pigs in the food industry) or even in food safety ?

What an interesting question!

I am a researcher at one of the many Max Planck Institutes in Germany, and the Max Planck Society (MPG) is mainly financed by public funds from the federal government and the federal states. Therefore, all research done within the MPG is published as scientific articles in journals and conferences and they are 100% open to the public. Some publishers have a paywall, but virtually all research and results can be accessed. I wouldn't know if anybody is out there reading these papers for a specific reason other than gaining scientific knowledge from them! :)

Thanks and hope this answers the question!
All the best,
/birgül

In addition to motility and engineerability, (both very important, most probably the most key features you need in this system) bacteria can sense and respond to changes in their local environment, providing a higher level of autonomy (such as chemotaxis, pH taxis and even magnetotaxis in the case of magnetotactic bacteria). Their size is also an important feature, being in the sub-micron to 2-3 micrometer range helps for better tissue filtration.

It is definitely not limited, and other bacterial species are currently being used in such studies as well. Especially prebiotic and probiotic bacteria (e.g., E. coli Nissle; EcN) is a promising strain as well.

I didn't get into the specific role of bacteria in cancer therapy but here is my all-time favorite review paper on the subject, where you can find out more about the use of various bacterial agents in cancer immunotherapy!: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802035/pdf/IJMICRO2016-8451728.pdf

All the best,

/birgül

Did you do any research which bottomed out, but you secretly think will be super relevant one day?

Hi Birgül!

I read that the mechanism for the treatment could be injections, considering that these are microorganisms alive and in high quantity, could they produce a high inmune response that reduce their ability to deliver the medicine?

It sound amazing!

How many of these nanobots do you think you could manufacture and is it expensive, and if so for what reasons? Could these hypothetically be used to do something like clear prions from the brain if you had enough of them, or could you make smaller ones? Thank you.

It is not dragging but rather aligning them. So what happens is that the nanoparticles on bacteria align with the applied magnetic field. Therefore, bacteria follow that path. We could also create so-called "magnetic gradients", which would cause dragging or pulling. But we want to use their own motility rather than pulling them.

As for the second question: No, they don't. We use electromagnetic coils (see: https://www.sciencedirect.com/topics/engineering/electromagnetic-coil) that generate enough magnetic field in the center of the setup to steer the microswimmers. These setups are designed for microscopic use, i.e., we attach them to a microscope to simultaneously visualize the motion of bacteria under magnetic fields. Of course, you would need much larger setups for use in humans in the future, but even in that case, it wouldn't be in contact with the body.

Thanks for the Qs!
All the best,
/birgül

thank you!!!

Do different wavelengths of light modify mitochondrial power output for microalgae or bacteria?

Great work on this answer, and even beyond it's quality I'm always pleased to see people acknowledging the difference between AI and ML. The former gets bandied about by so many folks in medicine and bioscience because they don't recognize that it's some collection of ML, logic processing, or other systems combined with an agent. I understand it's just a knowledge gap, but I think it's analogous to someone from outside biomed fields conflating basic bioscience and translational bioscience.

In practice I've even seen it hamper collaborations with true AI folks in other fields who might be great partners if they didn't have to be responsible for bridging the fields' "language" gap. Just a specific example of that more general issue on the biomed side, though, and something the education side of my work is focused on addressing.

This is a very important question! This is exactly why we are opting for a system that is active and externally controllable. Using a tiny machine that can be selective towards non-healthy tissue, that can be externally controlled to accumulate in a specific location (i.e., tumor) and that is equipped with an on/off switch to release its cargo on-demand are all the desired features in bacteriabots. This way, you minimize the side effects on non-target healthy cells. Realistically, it is almost impossible to cause no harm to a healthy cell even with an active controllable system. In that case, our bodies have defense mechanisms (immune system) that can fight unwanted agents. It is crucial to make sure that the bacteriabots are safe for administration below a certain dose and that they are not causing any pathological response.

All the best,
/birgül

Merhaba!

As I mentioned in another answer, bacteria should be removed from the host body after the medical task is completed, therefore another concept, which is named termination switches, could be also added to bacteria to terminate them after they had carried out their task through laser-triggered hyperthermia, antibiotics or bacterial lysis. If no such mechanism to remove them is in place, you would expect them to be neutralized by the immune system (granted that they are below a pathological dose). Since they are of cellular material, they are also fully biodegradable.

All the best,
/birgül

P.S.: I actually have a Turkish keyboard!

This is an amazing answer, thank you 👑

Thank you for your questions. Depending on the size and location of cancer, we would need millions to more than billions of them to localize and generate enough therapeutic effect.
Yes, they reproduce and multiply, which can be undesired for biohybrid bacterial agents, because reproducing means dilution of the synthetic components. That means new bacteria without enough magnetic material on them, causing loss of steerability. However, there are genetic tools that stop microorganism growth, which could be ideal here. Reproducing should also be under control because your injected dose could be in the millions range, but you could easily reach billions within a matter of hours, since the duplication time of microorganisms can be just minutes (e.g., around 20 minutes for E. coli). Additionally, bacteria should be removed from the host body after the medical task is completed, therefore another concept, which is named termination switches, could be also added to bacteria to terminate them after they had carried out their task through laser-triggered hyperthermia, antibiotics, or bacterial lysis.

All the best,
/birgül

Thanks for the question! Although I am no expert in bioremediation, I know that several large-scale wastewater treatments with microalgal technologies have already demonstrated the capability of detoxifying organic and inorganic pollutants. Microalgae can remove contaminants through three different pathways; bioadsorption, biouptake, and biodegradation. For further information I would recommend these publications:

https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btpr.3098

https://pubmed.ncbi.nlm.nih.gov/31382151/#:~:text=Microalgae%20have%20demonstrated%20potential%20for,%2C%20bio%2Duptake%20and%20biodegradation

Our research on microorganism based microrobotics mainly focuses on their medical functions, but I am always interested in finding out more on other uses of these tiny swimmers!

Hope I could answer your question!

All the best,

/birgül

Thank you for this interesting question! If we come to a point where these biological nano or microrobots are used in clinics, the treatment of hospital waste would technically become a concern. Once out of the body, the bacteria-based microrobots described in our study could easily be disposed of by sterilization techniques, such as using a detergent solution or by simply heating to sterilize. So you basically treat it as any other hospital waste.

I mentioned in another answer, so I am repeating that bacteria should be removed from the host body after the medical task is completed, therefore another concept, which is named termination switches, could be also added to bacteria to terminate them after they had carried out their task through NIR-triggered hyperthermia, antibiotics or bacterial lysis. THis way once the agents are outside of the body, they are already harmless.

Hope this answers your question!
All the best,
/birgül