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Assembly of large synthetic genomes using nanofluidics

Project description

Building genomes, one strand at a time

As synthetic biology advances, building complete genomes from scratch is becoming increasingly valuable for medicine, biotechnology, and environmental solutions. Synthetic genomics takes this further by assembling whole genomes from small DNA fragments, but efficiency drops as fragment size grows. This is mainly a physical issue: longer DNA strands are less likely to find and bind to each other. Overcoming this challenge is key to scaling genome synthesis. The ERC-funded SynGene project tackles this by using nanofluidic channels to stretch DNA and expose its ends for hybridisation. By harnessing yeast recombination machinery and short DNA templates, SynGene offers a powerful new method for manipulating entire genomes more effectively.

Objective

Synthetic genomics is a rapidly growing branch of synthetic biology where the goal is to assemble a complete genome from small synthetic DNA fragments. The main obstacle is the later stages of assembly where fragments on the kilobasepair length scale are to be assembled, where the efficiency rapidly falls off with increasing fragment size. A large contribution to this bottleneck is purely physical, where the probability of DNA ends meeting decreases with increasing DNA size. My solution to this problem is to force DNA ends to meet using nanofluidic channels. In such channels DNA is stretched out to almost the complete contour length, exposing the ends for hybridization. As part of my ongoing ERC-CoG, I have demonstrated several principles that will make it possible to use nanofluidic devices for genome assembly. Long DNA can be entropically trapped in nanochannels to force DNA ends to meet to promote hybridization of complementary overhangs. The bacterial protein Ku stably anneals 4 bp complementary overhangs, making it possible to engineer which fragments that are annealed. Bacterial Ligase D then binds to Ku to ligate the DNA.
Within this PoC project I will take the next steps to bring this principle to a commercially feasible platform.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

(opens in new window) ERC-2025-POC

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Host institution

CHALMERS TEKNISKA HOGSKOLA AKTIEBOLAG
Net EU contribution
€ 150 000,00
Address
-
412 96 Goteborg
Sweden
Region
Södra Sverige Västsverige Västra Götalands län
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Beneficiaries (1)