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| - | <p><b>Introduction</b><br>
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| - | Prokaryotes have been selected through evolutionary processes for accurate sensing
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| - | and acting upon their living environments. This bacterial versatility can be used by
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| - | us, humans, to sense the environments in places we have trouble reaching. Maybe we
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| - | would want to measure the conditions (e.g. nutrient availability, toxicity, pathogen
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| - | presence, light) somewhere deep under the ground, perhaps we would want to noninvasively
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| - | scan for biomarkers in diseased tissue in our bodies. The classical way
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| - | to make a bacteria tell us whether a certain event has happened is to link it to the
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| - | transcription of fluorescent proteins. This however requires constant monitoring and
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| - | maintenance in order to get an idea of the time-variation of the studied system. Could
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| - | we make the cell ‘remember’ what it has sensed and when so we can leave it alone for a
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| - | while and make it report back to us later?<br><br>
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| - | Meet E. memo, a ‘cellular logbook’, which uses the naturally occurring phenomenon
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| - | of <b>DNA methylation</b> to robustly store signals it has sensed in its environment. The
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| - | Amsterdam iGEM 2012 team, consisting of six students, will dedicate the summer to
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| - | the realization of this innovative and ambitious plan. This novel storage mechanism,
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| - | redesignating an evolutionarly designed tested and proven principle for novel purposes,
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| - | could be linked to any of the many biological sensors that are available in the DNA
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| - | parts registry. E. memo therefore holds great promise as a detect & store–system for
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| - | experimental and industrial purposes.<br><br>
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| - | Just storing whether certain signals have been sensed by the cell is only half of the story
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| - | however. The proposed memory mechanism would be a form of volatile memory,
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| - | of which the traces slowly dissappear as the E. memo-population keeps proliferating.
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| - | This is because methylation-patterns are not transferred to the progeny in eukaryotes.
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| - | We can use this our advantage. The most exciting part of our project would be to infer
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| - | when a signal has been sensed from the percentage of bits that is methylated, which
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| - | slowly decreases as the cells keep proliferating. This way, we won’t just store whether
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| - | a certain signal has occured; we will also know when it happened.<br><br>
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| - | <b>Molecular mechanism</b><br>
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| - | In short, we will introduce a site-specific methyltransferase into the iGEM default
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| - | chassis organism E. coli, that will only be active/transcribed when the measured signal
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| - | is encountered by the logbook-cell. The activated methyltransferase will then move
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| - | over to a plasmid region we’ve termed the bit and append a methyl-group to it. By
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| - | 1
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| - | linking the methyltransferase to a Zinc-Finger, its site-specificity is greatly increased,
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| - | reducing the amount of undesired background methylation events to a minimum.
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| - | Furthermore, by slowing down the cell replication cycle of the cells, we can increase
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| - | the span of time we can use to do measurements on.</p>
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