Difference between revisions of "Team:Fudan China/Description"
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<h2>Background - The era of cellular memory</h2> | <h2>Background - The era of cellular memory</h2> | ||
<p>We have already known it since we were little that memory is related to our mind and is able to store and retrieve our pasts. Now, biological memory has been defined as a sustained cellular response to a transient stimulus<sup>1</sup>. Cellular memory devices with cell or cell population have been developed in recent years. Some of them are based on transcriptional level, like toggle switch<sup>2</sup>, the others are based on DNA level by employing various recombinases<sup>3, 4</sup> or CRISPR<sup>5, 6</sup>. Although existing devices may have different functioning mechanism, they all share the same ability to store the past and retrieve it whenever we need. Here, we will introduce some existing memory devices and the potential usage of cellular memory before introducing our project.</p> | <p>We have already known it since we were little that memory is related to our mind and is able to store and retrieve our pasts. Now, biological memory has been defined as a sustained cellular response to a transient stimulus<sup>1</sup>. Cellular memory devices with cell or cell population have been developed in recent years. Some of them are based on transcriptional level, like toggle switch<sup>2</sup>, the others are based on DNA level by employing various recombinases<sup>3, 4</sup> or CRISPR<sup>5, 6</sup>. Although existing devices may have different functioning mechanism, they all share the same ability to store the past and retrieve it whenever we need. Here, we will introduce some existing memory devices and the potential usage of cellular memory before introducing our project.</p> | ||
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| + | <h3>Background - The era of cellular memory</h3> | ||
| + | <p>There are two types of devices in this category, toggle switches and positive-feedback loops. They all store the information by staying in a certain transcriptional state. Most of the devices here are mimics of circuits that have already existed in various organisms.</p> | ||
| + | <p>After the bacteriophage lambda switch was found, in 2000, a genetic toggle switch was firstly constructed in <i>Escherichia coli</i><sup>2</sup> as a memory device(Fig.1). With this repression loop, the transcriptional system switches between two stable states. As shown, the repression loop mainly consists of two components, promoters and repressors(known as transcriptional factor). Repressor1 inhibits Promoter1 from expressing Represser2 while Repressor2 inhibits Promoter2 from expressing Represser1. In other words, Represser1 and Represser2 are mutual antagonists, which means only one of them can be highly expressed. Without inducers, both of the states are possible. However, after the induction, things may change. For example, when Repressor1 is highly expressed, Inducer1 can stop the inhibition of Repressor1 and starts transcribing Repressor2. After that, Repressor2 represses Promoter2, thus decreasing the concentration of Represser1 and switching to another state. Furthermore, even if Inducer1 disappears after the transient induction, this state is stable. By adding a reporter following either of the repressors, we can retrieve the information whether the inducer has ever been existed. When using this device, both inducers are allowed to be customized to detect and memorize various events, such as DNA damage and quorum sensing<sup>7</sup>.</p> | ||
| + | <p>Another type of transcriptional-level-based memory device was designed later in <i>Saccharomyces cerevisiae</i>, which involves positive-feedback loops<sup>8, 9</sup>(Fig.2). This system is bistable as well. In one condition, Inducer1 does not exist. As a result, Reporter1 and Activator2 cannot be transcribed by Promoter1, making the positive-feedback loop untriggered. In another condition, Inducer1 induces the sensor and transcribes Activator2. Activator2 then binds to Promoter2, triggering the positive-feedback loop. After the trigger, Reporter2 will be expressed sustainedly in the absence of Inducer1. The information is stored. Similar to toggle switches, Inducer1 can be customized. For example, positive-feedback loop was designed to memorize the existence of high pheromone levels in budding-yeast<sup>10</sup>.</p> | ||
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Revision as of 06:48, 22 October 2017
Background - The era of cellular memory
We have already known it since we were little that memory is related to our mind and is able to store and retrieve our pasts. Now, biological memory has been defined as a sustained cellular response to a transient stimulus1. Cellular memory devices with cell or cell population have been developed in recent years. Some of them are based on transcriptional level, like toggle switch2, the others are based on DNA level by employing various recombinases3, 4 or CRISPR5, 6. Although existing devices may have different functioning mechanism, they all share the same ability to store the past and retrieve it whenever we need. Here, we will introduce some existing memory devices and the potential usage of cellular memory before introducing our project.
Background - The era of cellular memory
There are two types of devices in this category, toggle switches and positive-feedback loops. They all store the information by staying in a certain transcriptional state. Most of the devices here are mimics of circuits that have already existed in various organisms.
After the bacteriophage lambda switch was found, in 2000, a genetic toggle switch was firstly constructed in Escherichia coli2 as a memory device(Fig.1). With this repression loop, the transcriptional system switches between two stable states. As shown, the repression loop mainly consists of two components, promoters and repressors(known as transcriptional factor). Repressor1 inhibits Promoter1 from expressing Represser2 while Repressor2 inhibits Promoter2 from expressing Represser1. In other words, Represser1 and Represser2 are mutual antagonists, which means only one of them can be highly expressed. Without inducers, both of the states are possible. However, after the induction, things may change. For example, when Repressor1 is highly expressed, Inducer1 can stop the inhibition of Repressor1 and starts transcribing Repressor2. After that, Repressor2 represses Promoter2, thus decreasing the concentration of Represser1 and switching to another state. Furthermore, even if Inducer1 disappears after the transient induction, this state is stable. By adding a reporter following either of the repressors, we can retrieve the information whether the inducer has ever been existed. When using this device, both inducers are allowed to be customized to detect and memorize various events, such as DNA damage and quorum sensing7.
Another type of transcriptional-level-based memory device was designed later in Saccharomyces cerevisiae, which involves positive-feedback loops8, 9(Fig.2). This system is bistable as well. In one condition, Inducer1 does not exist. As a result, Reporter1 and Activator2 cannot be transcribed by Promoter1, making the positive-feedback loop untriggered. In another condition, Inducer1 induces the sensor and transcribes Activator2. Activator2 then binds to Promoter2, triggering the positive-feedback loop. After the trigger, Reporter2 will be expressed sustainedly in the absence of Inducer1. The information is stored. Similar to toggle switches, Inducer1 can be customized. For example, positive-feedback loop was designed to memorize the existence of high pheromone levels in budding-yeast10.
