By: Pooja Sharma
In a groundbreaking study, researchers have converted a natural bacterial immune system into the world’s smallest microscopic data recorder. By using the bacterial CRISPR/Cas immune system to generate miniature living tape recorders, scientists have successfully opened a new path to carry out environmental or microbiological sensing, diagnose diseases, develop future treatments, and record changes in body organs or systems— such as the gut. This new science has potentially paved the way for the future development of many new technologies.
What can these data recorders actually help to achieve?
These biologically engineered bacteria can record their interactions with the immediate environment. They can also encode the information about the events that occur in their surroundings. These cells are able to monitor the other invisible changes without disrupting those surroundings. It will be able to record changes that happen in body organs or body systems.
These bacteria can record whatever they do and how they interact with their environments, making it possible for the development of the future diagnosis and treatments to an otherwise difficult medical situation. This microscopic tape recorder can keep track of all the changes that take place in the bacterial environment. The best part, as mentioned above, is it can achieve such a major role without changing anything in the environment.
Harris Wang, Assistant Professor in the Department of Pathology and Cell Biology and Systems Biology at Columbia University Medical Centre said, “Such bacteria, when swallowed by a patient, might be able to record the changes they have experienced through the whole digestive tract, yielding an unprecedented view of previously inaccessible phenomenon”. He also led the new research and is the senior author of the group’s published paper in Science which is entitled ‘Multiplex recording of cellular events over time on CRISPR Biological Tape’.
What is a CRISPR?
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. It is a bacterial defense system and form the basis of the CRISPR-Ca9 genome editing technology. These systems can be used to target specific genetic codes and edit DNA at precise locations. This technology can be used to target certain genes in living organisms, and thus, correct certain mutations.
The bacterial CRISPR/Cas system is an example of a naturally occurring biological memory system. The cells CRISPR/Cas system cuts out short fragments of the foreign nucleic acid whenever a bacterium is infected by a genetic element. It, then integrates the sequence into the CRISPR spacers that are called as arrays. If, at any point in the future the same invader tries to infect the bacterium the second time, the immunity proteins can recognize and eliminate the invader. An important thing to note is the integration of foreign DNA occurs in a unidirectional fashion. This means that the CRISPR locus forms a chronological record of invading virus that passes down through bacterial generations.
The CRISPR/Cas is a natural biological memory device which is actually quite good from an engineering perspective. This is because the system has been naturally designed throughout the evolution to be really great at storing information.
The system that the researchers aimed to develop is actually something like a tape recorder. A tape recorder converts the temporary signals into recordable data written on the tape as it passes on through the recorder at a decided speed. The biological system is built pretty much around the same basis and is therefore called temporal recording in arrays by CRISPR expansion (TRACE).
CRISPR has been previously put to record and store books, poems and an experimental movie in DNA but this will be the first time it would be used to record cellular activity and trace and record its events. The authors have reported that using the CRISPR-Cas adaptation system to record biological signals and not simply sequence information of exogenous DNA has not been achieved till date. Within this framework, a biological input signal is first transformed into a change in the profuseness of a trigger DNA pool within the living cells. The spacer acquisition machinery is then employed to record the amount of trigger DNA into the CRISPR arrays in a unidirectional manner.
To achieve this bacterial recording system, the researchers used the laboratory strain of Escherichia coli to engineer two different plasmids. The first plasmid creates duplicates of itself in response to an external signal. The second plasmid accurately marks the time and expresses the required CRISPR/Cas system components. If, in case, there is no external signal the recording plasmid can insert the copies of the spacer sequence into the CRISPR locus.
When an external signal gets detected, the replicating plasmid becomes activated and inserts the signal sequences into the locus. The locus can then read using some computational tools. Initial tests within the TRACE system shows that the recorded information remains stable within the cell population for over 8 days.
Having a prototype system, the team demonstrates how it can easily be multiplied and helps them achieve a simultaneous recording of around three different signals – which in this case includes availability of metabolites like copper, trehalose and fructose – in the cell population environment over a period of three days. This work has easily enabled new application in biological recording. TRACE can be utilized to record metabolite fluctuations, gene expression changes, lineage associated information etc. It can help in getting information on difficult to study habitats such as the mammalian gut or open setting such as marine environment etc.
The team with Dr. Wang as the senior researcher is now planning to use the TRACE platform to investigate markers that indicate changes in normal or diseased states of gastrointestinal tract or any other bodily systems.