Team:Newcastle/Project

From 2013.igem.org

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=Project Overview=
=Project Overview=
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[[File:Synthetic_Biology_Cycle.png|500px|center]]
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[[File:SyntheticBiologyEngineeringLifeCycle.jpg|500px|center]]
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Synthetic Biology is a discipline which heavily employs engineering principles. One of these principles is the Engineering Lifecycle, a framework in which the project is split into clearly defined sections, based on the development of the project. These are, in sequential order: 1) Planning 2) Analysis 3) Modelling 4) Implementation 5) Testing.  After testing the cycle starts again, as we attempt to improve the system further.
+
Synthetic Biology is a discipline which heavily employs engineering principles. One of these principles is the Engineering Lifecycle, a framework in which the project is split into clearly defined sections, based on the development of the project. These are, in sequential order:
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Our team has worked within this framework throughout the project, as documented below: -
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#Requirements
 +
#Design (including Modelling)
 +
#Implementation
 +
#Verification
 +
#Maintenance
 +
#Refinement
 +
The cycle is iterated through again, as we attempt to improve the system further. We adhered to this cycle throughout our project including the development and characterisation of our BioBricks. This included modelling our BioBricks and sub-project outcomes before any experiments were conducted. This helped us better understand our engineered systems and predict the results of our ‘wet’ lab experiments.
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==Planning==
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Click on the links below to view each model or visit our [https://2013.igem.org/Team:Newcastle/Modelling/Introduction introductory modelling page]:
 +
*[https://2013.igem.org/Team:Newcastle/Modelling/L-form_Switch L-form switch]
 +
*[https://2013.igem.org/Team:Newcastle/Modelling/CellShapeModel Cell Shape]
 +
*[https://2013.igem.org/Team:Newcastle/Modelling/Cell_Fusion Cell Fusion]
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*[https://2013.igem.org/Team:Newcastle/Modelling/Hbsu_Fusion_Protein Hbsu-xFP]
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<!--In the process of deciding on a project for iGEM 2013 we've considered a multitude of ideas, including bacterial consortia against desertification, genomic encryption, anti-algal bacterial paint, and bacterial nano wires. Each of them was found to have its own strengths and weaknesses. For example bacterial consortia was a wonderful big idea, with a fundamental background from recent research, however due to the competition format and time limit on iGEM it was considered unreliable, where the level of input would have had little effect on the output due to the novelty of the subject, limited time and resourced to build such a system. The genomic encryption and nano wires ware not taken any further from the discussion at a number of meetings due to the lack of comprehensive information on the matters. While researching modern synthetic biology techniques we have found that a cell wall, one of the standard components of the bacterial cell may often cause difficulties in transformation efficiency, secretion of recombinant proteins, adapting to the environment etc. That is how the idea of removing a cell wall crossed our minds.-->
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==A Foundational Advance==
-
In the process of deciding on a project for iGEM 2013 we considered a multitude of ideas. These included the use of bacterial consortia to combat desertification, genomic encryption, anti-algal bacterial paint, and bacterial nano wires.  Each of these were found to have their own strengths and weaknesses. For example bacterial consortia to tackle desertification had the potential to transform deserts into agriculturally usable soil, and it also has a strong foundation of research to support its implementation. However, due to the novelty of the subject and the time constraints imposed by iGEM, it was decided that we would be unable to make a significant contribution to this subject area.
+
[[File:BareCillus_Switch.png|700px]]
-
The ideas of genomic encryption and nano wires were not fully developed due to concerns raised at team meetings around the lack of comprehensive information on these subjects.  While researching modern Synthetic Biology techniques we have found that a cell wall, one of the standard components of the bacterial cell, often causes difficulties in these techniques. These included transformation efficiency, secretion of recombinant proteins, adaption to the environment etc.  So we thought to ourselves: is there any way to remove the cell wall and still have a viable cell?
+
-
As a result we have developed a new chassis which we believe has the potential to revolutionise how Synthetic Biology is performed. The main [https://2013.igem.org/Team:Newcastle/Parts/l_form_switch BioBrick] that we have introduced enables the switching on and off of the bacterial cell wall in the model Gram positive bacteria ''Bacillus subtilis'', at the demand of the synthetic biologist, while still allowing cells to grow and divide.  Employing bacterial cells without a cell wall can both enable the synthetic biologist to explore new applications and research areas, and also build-upon and improve areas that are already being explored in Synthetic BiologyRather than the application-oriented nature of many iGEM projects, we think that the use of cell wall-less bacteria as a novel chassis in Synthetic Biology, as we propose, can benefit across the whole subject area, and furthermore be utilised as a tool to allow for even greater feats to be achieved by future iGEM teams.
+
While researching Synthetic Biology we found that a cell wall, one of the standard components of the bacterial cell, often causes difficulties in many techniques. These include transformation efficiency, secretion of recombinant proteins, adaption to the environment etcSo we thought to ourselves: is there any way to remove the cell wall and still have a viable cell?
-
<!--As a result of this we have found a project we believe to be destined to revolutionise the approach to synthetic biology by introducing a [https://2013.igem.org/Team:Newcastle/Parts/l_form_switch BioBrick] which would act as a switch for production and loss of bacterial cell wall in the model Gram positive bacteria ''Bacillus subtilis'' on our demand, while still allowing it to grow and divide. ''B. subtilis'' without a cell wall is better in many different ways and should be used as a new chassis for use in Synthetic Biology.-->
+
As a result we have developed a new chassis with the potential to revolutionize how Synthetic Biology is performed. The main [https://2013.igem.org/Team:Newcastle/Parts/l_form_switch BioBrick(BBa_K1185000)] that we have introduced enables the switching on and off of the bacterial cell wall in the model gram positive bacteria ''Bacillus subtilis'', at the demand of the synthetic biologist, while still allowing cells to grow and divide. Employing bacterial cells without a cell wall can both enable the synthetic biologist to explore new applications and research areas, and also build-upon and improve areas that are already being explored in Synthetic Biology. Rather than the application-oriented nature of many iGEM projects, we think that the use of cell wall-less bacteria as a novel chassis in Synthetic Biology, as we propose, can benefit across the whole subject area, and furthermore be utilised as a tool to allow for even greater feats to be achieved by future iGEM teams.
-
Bacteria which have lost their cell wall yet are still able to grow and divide are called L-forms, or as we prefer to call them, naked bacteria.  Take a look at our [https://2013.igem.org/Team:Newcastle/Project/L_forms L-form page] to familiarise yourself with L-form bacteria.  There are lots of things that can be achieved with naked bacteria, we explored a few of them:
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====[https://2013.igem.org/Team:Newcastle/Project/shuffling_endosymbiosis Genome Shuffling]====
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Bacteria which have lost their cell wall yet are still able to grow and divide are called L-forms, or as we prefer to call them, naked bacteria. If you would like to learn more about L-forms, please take a look at our [https://2013.igem.org/Team:Newcastle/Project/L_forms L-form page] or click [http://www.youtube.com/watch?v=b0Kk6bKKOQ0 here] to watch a short video summarising our project.
-
Fusion of bacteria is made significantly easier without a cell wall acting as a sheer physical obstacle. Cell fusion forces the fusants to reproduce sexually, where their genomes recombine. This can be used in genome shuffling, whereby genetic material is exchanged between the genomes of the fused cells.  Furthermore the process can be utilised through directed evolution, whereby certain characteristics that may be altered by this shuffling of genetic material are selected for.
+
Once we had created L-forms with our [https://2013.igem.org/Team:Newcastle/Parts/l_form_switch Switch BioBrick], we were unable to ignore the new opportunities that L-forms bring to Synthetic Biology:
-
====[https://2013.igem.org/Team:Newcastle/Project/plants Introduction and Detection of Naked Bacteria in Plants]====
+
====[https://2013.igem.org/Team:Newcastle/Project/shuffling_endosymbiosis Genome Shuffling]====
-
L-forms have been shown to form symbiosis in plants. Plants with naked bacteria show [https://2013.igem.org/Team:Newcastle/Project#References increased resistance to fungus] and they could be used to deliver useful compounds to the plant. This could give better crop yields, more nutritious harvests and reduce the need for spraying of fertiliser, pesticides or other compounds.
+
We investigated using genome shuffling and L-forms to artificially evolve ''B. subtilis''. Genome shuffling increases the rate of evolution, allowing the improvement of any biological system or phenotype in a feasible time frame. Over the past eight years iGEM teams have dreamt up innovative ways of harnessing Synthetic Biology. However this relatively new field faces challenges such as producing high quality yield of the desired product. Using L-forms allows the use of genome shuffling to solve this problem. If harnessed this could improve the efficiency of hundreds of iGEM projects as well as cell factories across the field of synthetic biology.
-
====[https://2013.igem.org/Team:Newcastle/Project/shape_shifting Shape Shifting]====
 
-
The loss of the cell wall leaves L-forms protected by only a cell membrane. The plasma membrane of L-forms is quite fluid. The advantage of this is that these cells would be able to adapt to shapes of various cracks and cavities, or will be able to "squeeze through" tiny channels and deliver cargo to hard-to reach targets.
+
[[File:BareCillus_Genome_shuffling.png|700px]]
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Click [http://www.youtube.com/watch?v=b0Kk6bKKOQ0 here] to view a short video which explains our project.
 
-
This isn’t a finite list of what can be done with naked bacteria, there’s loads more!  L-forms are currently used to discover novel antibiotics which don’t act on the cell wall.  L-forms can also teach us a great deal about how bacterial life has evolved, through acting as a model for a cell wall-less bacterial progenitor, and through being able to test the ease of induction of endosymbiosis in cell wall-less organisms [https://2013.igem.org/Team:Newcastle/Project#References (Mercier et al. 2013)].
+
====[https://2013.igem.org/Team:Newcastle/Project/plants Introduction and Detection of Naked Bacteria in Plants]====
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L-form bacteria can be used in any process which protoplasts are currently used for. Protoplasts are bacteria which have been chemically induced to lose their cell wall. They cannot however grow or divide (as L-forms can) and are not classified as being alive. L-forms can be used to transform bacteria which are recalcitrant to transformation [https://2013.igem.org/Team:Newcastle/Project#References (Chang and Cohen 1979)].
+
We successfully inoculated HBsu-GFP tagged L-forms into ''Brassica pekinens'' (Chinese Cabbage). L-forms have been shown to form symbiotic relationships in plants such as Chinese Cabbage and strawberries. Plants with naked bacteria show [http://www.ncbi.nlm.nih.gov/pubmed/11849491 increased resistance to fungus] and L-forms could be engineered to deliver useful compounds to crops; an artificial symbiotic relationship. In the future L-forms could be engineered to provide their host plants with beneficial compounds such as nitrogen, plant hormones or anti-fungals. This could give better crop yields, more nutritious harvests and reduce the need for spraying of fertilizer or pesticides. Crucially, we have shown that L-forms will burst if they are not in an osmotically stable environment. This makes them a better delivery system than cell walled bacteria as they will die if they exit their host plant.
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One crucially important feature of our naked bacteria is that they are osmotically sensitive, meaning that they will lyse if they escape into the environment. This means that they can be used in non-contained environments (e.g. agriculture).
 
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==Analysis==
 
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Each of our chosen research themes has had a set of specific requirements, i.e. BioBricks, equipment and, of course, a research strategy.
 
-
 
-
====[https://2013.igem.org/Team:Newcastle/Project/shuffling_endosymbiosis Genome Shuffling]====
 
-
 
-
To explore the possibilities of using L-forms of ''B. subtilis'' for inducing the exchange of DNA fragments between related bacteria we have designed two BioBricks to differentially tag the DNA of different cells with fluorescent proteins.  in order to visually witness the fusion events and reliably analyse the collected data. The BioBricks were designed without a promoter, so they could be cloned into any plasmid under the control of the desired promoter and be used in various bacterial species.
 
-
 
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For our research we used pMutin4 plasmids. However before deciding to use this particular plamid we have tested a plasmid designed by the Groningen 2012 iGEM team. We were unable to use the plasmid and we have thus managed to [http://parts.igem.org/Part:BBa_K818000:Experience characterise it] and speculate why this part is non-functional.
 
-
 
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====[https://2013.igem.org/Team:Newcastle/Project/plants Introduction and Detection of Naked Bacteria in Plants] ====
 
 +
[[File:BareCillus_Plant_infographic.png|700px]]
====[https://2013.igem.org/Team:Newcastle/Project/shape_shifting Shape Shifting]====
====[https://2013.igem.org/Team:Newcastle/Project/shape_shifting Shape Shifting]====
-
The loss of the cell wall leaves L-forms protected by only a cell membrane. The plasma membrane of l-forms is quite fluid. The advantage of this is that these cells would be able to adapt to shapes of various cracks and cavities, or will be able to "squeeze through" tiny channels and deliver cargo to hard-to reach targets.
 
-
We have planned to test this hypothesis by injecting the naked bacteria into specially designed microfluidics chambers and observing their behaviour under the microscope. Membrane would have been visualised with a commonly used membrane stain F.595
+
The loss of the cell wall leaves L-forms protected by only a fluid cell membrane. The advantage of this is that these cells would be able to adapt to shapes of various cracks and cavities, or will be able to "squeeze through" tiny channels and deliver cargo to hard-to reach targets.
 +
To explore the potential for L-forms in this area, we intended to manipulate them using microfluidics. For this we created microfluidics chips using autoCAD. We have laid the foundations for future iGEM teams to further explore the biophysical properties of bacterial cell membranes.
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==Modelling==
 
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The next step on the diagram is modelling. This step is an essential part of a successful synthetic biology project. Although it requires a lot of time and effort, and therefore is often neglected. We believe that in the long run modelling can save a lot of time, effort and resources to those who take their time in the beginning, simulating all the possible outcomes of the system and refining it at an early stage, before any ''in vitro'' and ''in vivo'' experiments have been planned and conducted. Another positive side to modelling prior to the "wet lab" sessions is the fact that a model behaves according to the known facts and principles, and if in real life the outcome drastically differs from the simulation, there's a good chance of finding out what may be causing the difference through adjusting the model and repeating the experiments.
 
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For every research theme we have constructed a model to help us understand the systems we engineered. Click on the links to view each model or visit our [https://2013.igem.org/Team:Newcastle/Modelling modelling page]:
 
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*[https://2013.igem.org/Team:Newcastle/Modelling/L-form_Switch L-form switch]
 
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*[https://2013.igem.org/Team:Newcastle/Modelling/CellShapeModel Cell Shape]
 
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*[https://2013.igem.org/Team:Newcastle/Modelling/Cell_Fusion Cell Fusion]
 
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*[https://2013.igem.org/Team:Newcastle/Modelling/Hbsu_Fusion_Protein Hbsu-xFP]
 
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==Implementation==
 
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What we've done for each project (brief summary). Assuming the same format as Analysis.
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[[File:Shape shifting copy.jpg|700px]]
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==Testing==
 
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This is the section where the summary of our results goes.
+
This isn’t a finite list of what can be done with naked bacteria, there’s loads more!  L-forms are currently used to discover novel antibiotics which don’t act on the cell wall.  L-forms can also teach us a great deal about how bacterial life has evolved, through acting as a model for a cell wall-less bacterial progenitor, and allowing testing of induction of endosymbiosis in cell wall-less organisms [https://2013.igem.org/Team:Newcastle/Project#References (Mercier et al. 2013)].  
-
We were successful in creation of a [https://2013.igem.org/Team:Newcastle/Parts/l_form_switch BioBrick which allows the switching on and off of the cell wall of ‘’B.subtilis”].
 
-
[https://2013.igem.org/Team:Newcastle/Project/shuffling_endosymbiosis We have shown the recombination of the L-forms' genomes as a result of fusion].
+
In addition to our work above, we characterized [http://parts.igem.org/Part:BBa_K818000:Experience Part: BBa_K818000] showing that it does not work in ''B. subtilis''. We then sequenced this part, noted that its sequence differed from its entry on the iGEM registry and created a new registry page for [http://parts.igem.org/Part:BBa_K1185004 Part: BBa_K1185004] with the correct sequence.
-
We’ve shown that the naked bacteria that we created using our [https://2013.igem.org/Team:Newcastle/Parts/l_form_switch switch BioBrick] also [https://2013.igem.org/Team:Newcastle/Project/plants#Results form these associations].
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====[https://2013.igem.org/Team:Newcastle/Architecture Architecture]====
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All you need to start using an [https://2013.igem.org/Team:Newcastle/Project/L_forms L-form] chassis is a culture of ''Bacillus subtilis'', our [https://2013.igem.org/Team:Newcastle/Parts/l_form_switch L-form switch BioBrick] and a [https://2013.igem.org/Team:Newcastle/Notebook/protocols set of instructions] from us.
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Because Synthetic Biology applies engineering techniques to biology, it makes it’s design cycle very similar to architecture and modelling is a very important stage in the design cycle of both fields.  Just like we used models in our project to predict outcomes, computer aided design modelling is used in architecture. This got us thinking about other similarities and differences in the design cycle. We then speculated on the possible ways we could apply Synthetic Biology to architecture and the effect the two fields may have on each other in the future.
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<!--
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[[File:Arch_copy.jpg|600px]]
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==[https://2013.igem.org/Team:Newcastle/Project/shuffling_endosymbiosis Genome Shuffling]==
+
-
Fusion of bacteria is made significantly easier without a cell wall. This forces the fusants to reproduce sexually, where their genomes recombine, and this can be used in directed evolution. [https://2013.igem.org/Team:Newcastle/Project/shuffling_endosymbiosis We have shown L-forms fusing, and the recombination of their genomes].
+
-
-->
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-
<!--
+
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==[https://2013.igem.org/Team:Newcastle/Project/plants Introduction and Detection of Naked Bacteria in Plants] ==
+
-
L-forms have been shown to form symbiosis in plants.  We’ve shown that the naked bacteria that we created using our [https://2013.igem.org/Team:Newcastle/Parts/l_form_switch switch BioBrick] also [https://2013.igem.org/Team:Newcastle/Project/plants#Results form these associations]. Plants with naked bacteria show [https://2013.igem.org/Team:Newcastle/Project#References increased resistance to fungus] and they could be used to deliver useful compounds to the plant. This could give better plant yields, more nutritious plants and reduce the need for spraying of fertiliser, pesticides or other compounds.
+
-
-->
+
-
<!--
+
-
==[https://2013.igem.org/Team:Newcastle/Project/shape_shifting Shape Shifting]==
+
-
The loss of the cell wall leaves L-forms protected by only a cell membrane. The plasma membrane of l-forms is quite fluid. The advantage of this is that these cells would be able to adapt to shapes of various cracks and cavities, or will be able to "squeeze through" tiny channels and deliver cargo to hard-to reach targets.
+
-
We were planning to test this hypothesis by injecting the naked bacteria into specially designed microfluidics chambers and observing their behaviour under the microscope. However due to time and logistics constraints we were unable to do it. For more information please visit [https://2013.igem.org/Team:Newcastle/Project/shape_shifting shape shifting page]
 
-
-->
 
==References==
==References==

Latest revision as of 17:57, 28 October 2013

 
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IGEM Home Newcastle University

Contents

Project Overview

SyntheticBiologyEngineeringLifeCycle.jpg

Synthetic Biology is a discipline which heavily employs engineering principles. One of these principles is the Engineering Lifecycle, a framework in which the project is split into clearly defined sections, based on the development of the project. These are, in sequential order:

  1. Requirements
  2. Design (including Modelling)
  3. Implementation
  4. Verification
  5. Maintenance
  6. Refinement

The cycle is iterated through again, as we attempt to improve the system further. We adhered to this cycle throughout our project including the development and characterisation of our BioBricks. This included modelling our BioBricks and sub-project outcomes before any experiments were conducted. This helped us better understand our engineered systems and predict the results of our ‘wet’ lab experiments.

Click on the links below to view each model or visit our introductory modelling page:

A Foundational Advance

BareCillus Switch.png

While researching Synthetic Biology we found that a cell wall, one of the standard components of the bacterial cell, often causes difficulties in many techniques. These include transformation efficiency, secretion of recombinant proteins, adaption to the environment etc. So we thought to ourselves: is there any way to remove the cell wall and still have a viable cell?

As a result we have developed a new chassis with the potential to revolutionize how Synthetic Biology is performed. The main BioBrick(BBa_K1185000) that we have introduced enables the switching on and off of the bacterial cell wall in the model gram positive bacteria Bacillus subtilis, at the demand of the synthetic biologist, while still allowing cells to grow and divide. Employing bacterial cells without a cell wall can both enable the synthetic biologist to explore new applications and research areas, and also build-upon and improve areas that are already being explored in Synthetic Biology. Rather than the application-oriented nature of many iGEM projects, we think that the use of cell wall-less bacteria as a novel chassis in Synthetic Biology, as we propose, can benefit across the whole subject area, and furthermore be utilised as a tool to allow for even greater feats to be achieved by future iGEM teams.

Bacteria which have lost their cell wall yet are still able to grow and divide are called L-forms, or as we prefer to call them, naked bacteria. If you would like to learn more about L-forms, please take a look at our L-form page or click [http://www.youtube.com/watch?v=b0Kk6bKKOQ0 here] to watch a short video summarising our project.

Once we had created L-forms with our Switch BioBrick, we were unable to ignore the new opportunities that L-forms bring to Synthetic Biology:

Genome Shuffling

We investigated using genome shuffling and L-forms to artificially evolve B. subtilis. Genome shuffling increases the rate of evolution, allowing the improvement of any biological system or phenotype in a feasible time frame. Over the past eight years iGEM teams have dreamt up innovative ways of harnessing Synthetic Biology. However this relatively new field faces challenges such as producing high quality yield of the desired product. Using L-forms allows the use of genome shuffling to solve this problem. If harnessed this could improve the efficiency of hundreds of iGEM projects as well as cell factories across the field of synthetic biology.


BareCillus Genome shuffling.png


Introduction and Detection of Naked Bacteria in Plants

We successfully inoculated HBsu-GFP tagged L-forms into Brassica pekinens (Chinese Cabbage). L-forms have been shown to form symbiotic relationships in plants such as Chinese Cabbage and strawberries. Plants with naked bacteria show [http://www.ncbi.nlm.nih.gov/pubmed/11849491 increased resistance to fungus] and L-forms could be engineered to deliver useful compounds to crops; an artificial symbiotic relationship. In the future L-forms could be engineered to provide their host plants with beneficial compounds such as nitrogen, plant hormones or anti-fungals. This could give better crop yields, more nutritious harvests and reduce the need for spraying of fertilizer or pesticides. Crucially, we have shown that L-forms will burst if they are not in an osmotically stable environment. This makes them a better delivery system than cell walled bacteria as they will die if they exit their host plant.


BareCillus Plant infographic.png

Shape Shifting

The loss of the cell wall leaves L-forms protected by only a fluid cell membrane. The advantage of this is that these cells would be able to adapt to shapes of various cracks and cavities, or will be able to "squeeze through" tiny channels and deliver cargo to hard-to reach targets. To explore the potential for L-forms in this area, we intended to manipulate them using microfluidics. For this we created microfluidics chips using autoCAD. We have laid the foundations for future iGEM teams to further explore the biophysical properties of bacterial cell membranes.


Shape shifting copy.jpg


This isn’t a finite list of what can be done with naked bacteria, there’s loads more! L-forms are currently used to discover novel antibiotics which don’t act on the cell wall. L-forms can also teach us a great deal about how bacterial life has evolved, through acting as a model for a cell wall-less bacterial progenitor, and allowing testing of induction of endosymbiosis in cell wall-less organisms (Mercier et al. 2013).


In addition to our work above, we characterized [http://parts.igem.org/Part:BBa_K818000:Experience Part: BBa_K818000] showing that it does not work in B. subtilis. We then sequenced this part, noted that its sequence differed from its entry on the iGEM registry and created a new registry page for [http://parts.igem.org/Part:BBa_K1185004 Part: BBa_K1185004] with the correct sequence.

Architecture

Because Synthetic Biology applies engineering techniques to biology, it makes it’s design cycle very similar to architecture and modelling is a very important stage in the design cycle of both fields. Just like we used models in our project to predict outcomes, computer aided design modelling is used in architecture. This got us thinking about other similarities and differences in the design cycle. We then speculated on the possible ways we could apply Synthetic Biology to architecture and the effect the two fields may have on each other in the future.


Arch copy.jpg

References

[http://www.ncbi.nlm.nih.gov/pubmed/11849491 Walker R, Ferguson CMJ, Booth NA and Allan EJ (2002) The symbiosis of Bacillus subtilis L-forms with Chinese cabbage seedlings inhibits conidial germination of ‘Botrytis cinerea. Letters in Applied Microbiology, 34, 42-45.]

[http://www.ncbi.nlm.nih.gov/pubmed/107388 Chang S and Cohen SN (1979)High frequency transformation of Bacillus subtilis protoplasts by plasmid DNA. Molecular Genetics & Genomics, 168, 111–115.]

[http://www.cell.com/abstract/S0092-8674(13)00135-9 Mercier R, Kawai Y and Errington J. (2013) Excess Membrane Synthesis Drives a Primitive Mode of Cell Proliferation, Cell, 152, 997–1007.]


Newcastle University The Centre for Bacterial Cell Biology Newcastle Biomedicine The School of Computing Science The School of Computing Science