Posts Tagged “quorum sensing”

This post on Microbe World entitled: “Software for Programming Microbes” did attract my attention, and I followed its source in the MIT Technology Review: An amazing article presenting a fascinating newly emerging technology of programming bacteria to do whatever we want them to do, produce drugs more efficiently, clean up oil spills, anything… useful! But the methodology was quite beyond my imagination.

I was extremely lucky to be able to interview Dr. Christopher Voigt, Associate Professor at the University of California, San Francisco, who is the project leader. Dr. Voigt has published over 34 articles indexed in Pubmed and you can find more about his projects on his lab website.

Now I will leave you with the interview! I thank Radwa for reviewing it.

Dr. Christopher Voigt

Dr. Christopher Voigt

1. May you please simplify the term “genetic circuit” to the micro-readers? What drove you to use software to genetically modify bacteria?
A genetic circuit functions like an electronic circuit, but uses biochemical interactions to do the computation. I am a computer programmer at heart and find living cells to be the ultimate challenge.
2. We used to hear a lot about the use of genetically modified bacteria in cleaning up toxicants or oil spills, producing drugs and biofuel. How is “programming bacteria” different from the “regular” definition of genetic engineering, which might be based on inserting a gene, a regulatory gene, or an operon that encodes for a certain needed functionality?
Genetic programming controls the timing and conditions under which those processes occur.  It doesn’t refer to the pathways by which molecules are made or degraded.
3. In MIT Technology Review, you mentioned that like for a computer, programming bacteria is about writing a program to be encoded on a piece of DNA to implement a function. How can bacterial cells understand the code? How can the software make them sense the outer media?
The DNA contains codes for when molecules like proteins and mRNA should start and stop being produced and under what conditions. A protein can change its state when it senses a condition and bind to DNA to cause genes to be turned on or off.  This acts like a sensor.
4. Honestly, I can’t imagine writing a piece of code to link bacterium to one another, because node->pRight!=NULL ? I just can’t imagine it. Is there any risk of overloading natural functions by accident?
No.
5. How can programing bacteria make use of quorum sensing?
Quorum signaling enables cells to be programmed to communicate with each other.
6. How can drug discovery and production benefit from programmable bacteria in the near future?
It makes it easier to access and control those pathways.
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Forget about the old Petri dishes and culture media! A brilliant new method for the growing of microorganisms in order to study their behavior, especially in a large community, again tracking the phenomenon of quorum sensing , has been developed and put to use.

The new invention, by Connell et al., resembles a trapping sack for microorganisms, made of bovine serum albumin covalently cross-linked by laser lithography to form a three dimensional structure. These harboring chambers are very small, with a 2 to 6 picoliter capacity, and are permeable, and thus allowing an infinite influx of nutrients and other essential small molecules for the bacteria growing inside.

Scientists have already compared the growth rates of Pseudomonas cells in “the trap sacks” to those in conventional culture media and mouse lungs and the results were promising! The new technique allows them to study patterns of antibiotic resistance, infection and biofilm formation more clearly and in earlier phases of bacterial growth…

Source: Science magazine, Vol. 330 issue 6004.

Image source: Microbiology Bytes

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Meeting a scientist is like reading many books in few minutes, books of science and books of life. To me, though, meeting Dr. Niyaz Ahmed (1) was like reading a library. He is one of the most active advocates for Open Access (OA) and open evaluation of science. His support for OA is not just by words, but through sharing effectively in such purpose as he is a section editor of Microbiology and Genomics in PLoS ONE and a chief editor in Gut pathogen, the official journal of ISOGEM (the International Society for Genomic and Evolutionary Microbiology), in Sassari, Italy, of which Dr. Ahmed is a co-founder and the General Secretary. ISOGEM members work on developing post-genomic ideas to serve the public health and the environment. Dr. Ahmed is one of the faculty members of Faculty of 1000 Biology, the expert guide to the most important advances in biology.

Dr. N. Ahmed’s early start was in India as he graduated in Veterinary Medicine and obtained his Masters degree in Animal Biotechnology, then his PhD in Molecular Medicine. Currently, he is also based in India, in Hyderabad University as an Associate Professor of Biotechnology and a staff scientist in the Center of DNA Fingerprinting and Diagnostics in Hyderabad. This is not everything about him, his homepage reveals more, especially those pioneer achievements in the research world in India, like being a co-principal investigator of the Mycobacterium W genome program, India’s first whole genome sequencing project, and the most amazing part of his research is working on Helicobacter pylori chronological evolution and phylogeographic analysis.

Having read about all these achievements, I had many questions in mind, but, knowing how busy he is,  I tried to reduce them to the following few questions that cover different areas of his activities.  Dr. Ahmed generously agreed to answer them all.

Dr. Niyaz Ahmed, any microbiologist would be honored to meet you, and so am I. I am one of the “Micro Writers” blog members; we are young enthusiastic students from Faculty of Pharmacy, Cairo University in Egypt, mostly undergraduate and some graduate students, who are looking from the blog window towards the research world. Most of us wished someday to become scientists; “Micro Writers” is like the first real step on the right way. Our blog focuses on different areas of microbiology. It is like a message by students so far from Egypt, but hopefully from other places as well, to students all over the world. I read a lot about your achievements, especially those concerning the H. pylori phylogeographic analysis. As you have a great experience in research, reviewing articles and especially because you own a blog, I would like to ask you a few questions, and get them published with your answers on the blog, in order to teach and guide not only us, but the all students from everywhere.

  • N.A.: I am very much enthused by your offer and would like to be interviewed at Micro-Writers blog. Please let me know your questions and I would try to answer them all.

Since you are working on the population structure of H. pylori, and on their chronological evolution, can the phylogeographic analysis of bacterial strains lead to infection control or innovative treatment? If yes, how?

  • N.A: It may not directly lead to product development as such, but, it can definitely explain how the spread-patterns of this organism are? and that has a lot of bearing on infection control in terms of tracking the infection sources. Also, knowing separate lineages in greater details offers accurate diagnostic development which in turn helps keep a tab on their emergence or otherwise.

If phylogeographic analysis can teach us about migration of some strains from one place to another, can we use it in a reverse way? I mean can we use this analysis to learn about the origin of mankind, and his migration routes?

  • N.A.: Indeed, we can do that. For a bacterial parasite to become a surrogate marker of human history (including migrations), it needs that its population structure mimics with that of the host. It is now established that H. pylori has most probably coevolved with its human host and thus its population structure is juxtapose to the human population structure. Therefore, we can use it as a marker of human history and geography.

Concerning the unpublished ideas of your studies, which suggest that bacterial proteins may be able to perform both the immune stimulatory and immune evasion tasks, the simple question is, do you think bacteria are smart? Do they have that smart controlling machinery that is able to distinguish between all these factors?

  • N.A.: The term ‘smart’ is reserved for humans. However, we can say that bacteria are highly adaptable. Several bacterial traits such as quorum sensing, community interactions (such as that seen in biofilm formation), molecular mimicry, immune evasion, dormancy etc. definitely point towards their being ‘intelligent’.

You talked about the host-pathogen relationship. I would like to add one more suggestion, which is that bacteria may face the immune system or the host body as a community of workers, not as independent cells. It is like the idea of sociomicrobiology in biofilms. Does this social behavior apply to other communities of bacteria other than bioflims, e.g. the community of H. pylori cells against the human defense system in the stomach?

  • N.A.: Indeed there is a body of evidence coming in via both in vitro and in vivo observations that H. pylori cells tend to form biofilms which is favored by gastric mucin and by mutations of luxS, and the cagE type IV secretion gene. This observation is important to understand H. pylori’s resistance to host immune responses and antibiotics, and in microenvironmental pH homeostasis which conditions and streamlines the growth and survival of H. pylori in vivo.

You mentioned at your homepage that strains of H. pylori in the Southern Asia are not life-threatening in the same time they may cause gastric cancer in the West. Do you think the lifestyle in Southern Asia, especially the food (extra-spicy food), might lead to evolution of these non-lethal strains, and vice versa in case of the western lifestyle?

  • N.A.: It is observed that high incidence of H. pylori in India (nearly 98%) does not positively correlate with the rates of invasive outcomes and life-threatening consequences of the infection (cancer). It is possible that the food that is eaten here (rich is herbs and vegetables) has some protective advantage in terms of governing the micro-environmental conditions at the niches colonized by H. pylori. Another aspect is genetic susceptibility or resistance to gastric cancer which is to be considered as well.

Adoption of open access (OA) in science, isn’t it a huge responsibility, with great challenges, most probably the funding challenge? I mean, who will pay always for open access science?

  • N.A.: Open Access is a reality and the most practical approach to augment knowledge sharing towards science education, research and the practice of medicine and agriculture. Developing countries that have brains but no library budgets and that have been until now deprived of access to knowledge will be at a great benefit with this OA revolution. I do not see any challenge here as funding agencies such as NIH, Howard-Hughes Institute and Welcome Trust have already started subsidizing costs for OA in a big headway.

You started in India; did you feel some bias (in the international journal publishing) towards some western countries (e.g., USA, Germany, France, UK, etc.)? Do you think that the researchers from the developing countries should be encouraged in a way or another, especially against the fees and restrictions of publishing?

  • N.A.: I firmly believe that originality and novelty have no barriers. If your ideas are novel and your findings well defended, no one can stop them from seeing light of the day. Developing country scientists are equally respected – I can cite my own example, I was made Section Editor at PLoS ONE to oversee an extremely important area, microbial genomics; for this appointment, my affiliation and my geographical co-ordinates were not the important criteria but my standing in the field of medical microbiology, the efficiency with which I handled the issues and my professional commitment to the cause and ethos of OA publishing. However, there may be exceptions of which I have no idea. Nevertheless, this is a free world and if one has zeal and dedication, success is not that far. These days, publication restrictions based on novelty or being on ‘cutting edge’ or otherwise, are no issues. Developing country scientists are thus free to bring forward their research even on topics which may not be interesting to a few ‘glamour magazines’ of science, but they are welcome at descent venues such as PLoS ONE; they are free to even send in aspects of their folklore medicine, their local environmental problems, cropping, local biodiversity, energy production, their cultural and human anthropological aspects (and topics cutting across these) wherein no one is their competitor! Fees for publication is not a problem, PLoS and Biomed Central both waive off publication charges quite generously in almost all cases of genuine inability to pay.

In an old interview, you said that blogs are a good chance for young scientists to express their ideas for free, what about the older scientists in the developing countries who need more space to express their research activities, in the same time so many restrictions are imposed on them to get their papers published in the international journals?

  • N.A.: Old, and young, all need to be part of the dialogue. Even for busy academics, blogs are extremely helpful although they are no alternative to a proper publication of results or viewpoints. Blogs can effectively blend zeal and enthusiasm of ‘young Turks’ with the experience and patient advice of the ‘old guards’. Academic institutions in the developing countries should support such portals wherein students and faculty discuss research to arrive on novel interpretations and provocative ideas in an interdisciplinary environment of learning and enabling.

As an editor and reviewer in so many journals, what is your advice to some young Egyptian researchers like us in the “Micro Writers” blog who work with the fewest capabilities and with minimal resources, to get our papers published in an easier way?

  • N.A.: I love the Micro Writers Blog. You are the torch-bearers for all other undergraduate students in our countries of the developing world. My advice is try hard to deliver your best. Do not write on complaints – write about solutions! Do not present as Egyptian, or African, think globally, be a part of global community in the best interests of humanity, the environment and wellbeing of all creatures. I can quote from the Holy Qur’an: “Wallatheena Jaahadu Feena Lanahdiyannahum subulana” (The more you dedicate yourself and strive hard, the more will be the opportunities and paths widened for you from the Almighty). (2)

 

Finally, I would like to thank you Dr. Niyaz for the time you gifted for us to answer my questions with plentiful ideas, objects, and words. I am quite sure, each one who reads this interview will get benefited more than once.

Dr. Niyaz Ahmed

Dr Niyaz Ahmed (left) co-ordinating a ‘student-scientist-administration’ meeting with Nobel Laureate Prof. Peter C. Doherty (center) and Australian High Commissioner to India, Mr John McCarthy (right).

 

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(1): Dr Niyaz Ahmed, PhD

General Secretary,  ISOGEM
Section Editor, PLoS ONE
Chief Editor, Gut Pathogens
Assoc. Editor, Ann Clin Microb Antimicrobials
Assoc. Editor, Acta Veterinaria Scandinavica
Faculty Member, Faculty of 1000 Biology
Corres. Fellow, Eur Helicobacter Study Group

 

(2): EL-Qur’an El-Karim, chapter #29 (El-Ankaboot), verse #69.

Image credits: Dr. Niyaz Ahmed.

 


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