iGEM – the heart of synthetic biology 

Over 400 teams from across the globe con­vene in Paris to show­case the out­comes of their year-long pro­jects. The iGEM Mu­nich team is made up of stu­dents from vari­ous disci­plines, in­clud­ing mo­lecu­lar biolo­gy, bioin­for­mat­ics, and medi­cine, repre­sent­ing the two lead­ing uni­versi­ties in Mu­nich, LMU and TUM. This year, the team also in­clud­ed stu­dents from the Elite Graduate Pro­grams "Hu­man Biol­ogy – Prin­ciples of Health and Dis­ease" and "Re­spon­sibil­ity in Sci­ence, Engi­neer­ing, and Tech­nolo­gy".

In 2024, iGEM Mu­nich de­veloped Pro­gRAM: Pro­grammable RNA Ac­cess Memory. Our pro­ject aimed to give cells the ability to record events hap­pen­ing inside them, turn­ing them into their own chronol­ogists. How­ever, most exist­ing sys­tems to date rely on DNA, the "hard drive" of the cell, which makes ac­cess­ing and read­ing the rec­orded in­for­mation both time-consum­ing and dis­rup­tive.

To over­come these chal­leng­es, we drew inspi­ration from how ran­dom access memory works in com­put­ers – allow­ing for rapid stor­age and re­trieval of data. RNA, as the cell's mes­sen­ger, could play a simi­lar role in mo­lecu­lar re­cord­ing. We used a dead Cas13b en­zyme fused with an RNA deam­inase do­main (ADAR) to write on the RNA. Upon sens­ing a cellu­lar event, a gRNA is ex­pressed to guide the edit­ing com­plex to its target. When on target, the ADAR do­main cata­lyzes the deam­ina­tion of aden­osine to ino­sine within a syn­thetic re­cord­ing tape. The de-am­ina­tion pro­cess inac­tivates a start co­don, caus­ing a frameshift and trig­gering the ex­pres­sion of a re­porter in one of three frames, de­pend­ing on the rec­orded state. It cre­ates a „traf­fic light sys­tem”, allow­ing moni­toring the rec­orded state while pre­serv­ing cell integ­rity.

But iGEM is much more than just wet lab and dry lab! Over the past year, we’ve worked hard to bring syn­thetic biolo­gy closer to the gen­eral pub­lic. Rec­ogniz­ing the grow­ing influ­ence of AI, we orga­nized an inter­disci­pli­nary panel dis­cussion on its future role in mod­ern biolo­gy. Our edu­cational out­reach also in­clud­ed events like Girls' Day, iGEM@school, Bioin­for­matics Day, and the TUM and LMU Open Days, where we intro­duced 3D-printable puz­zles ex­plain­ing the cen­tral dog­ma of mo­lecu­lar biolo­gy.

In addi­tion, we de­veloped the iGEM Data Ex­plorer, a cus­tom AI-powered tool de­signed to make the vast scien­tific con­tent in iGEM wikis more acces­sible and inter­ac­tive. With over 4,470 wikis to ex­plore, exist­ing tools pro­vide only sur­face-level de­tails, miss­ing the depth of work done by previ­ous iGEM teams.

Dur­ing our time at the Grand Jam­boree in Paris, we had the op­por­tunity to pre­sent our pro­ject to teams from around the world, as well as to ex­perts from aca­demia and indus­try, through two Live Stage Presenta­tions and Booth ses­sions. We are proud to share that our ef­forts re­sulted in a Gold Medal and a nomi­nation for the Best Soft­ware tool! Our jour­ney could not have been possi­ble with­out the sup­port of our spon­sors, which in­clud­ed the Elite Net­work of Ba­varia.

You can find more details about ProgRAM on our wiki: https://2024.igem.wiki/munich/.

Text:  Natalia Kuźmierkiewicz, Elite Graduate Program "Human Biology - Principles of Health and Disease"