Nygård Group

Synthetic transcriptional control device expressed in fungi. Picture from Mozsik et al., 2019.Synthetic transcriptional control device expressed in fungi. Picture from Mozsik et al., 2019.

The overall aim of our research is to accelerate the design-build-test-learn cycle for making novel or improved cell factories for converting lignocellulosic biomass (industrial side-streams coming from plant residues) or sugars into platform or precision chemicals. Examples of target products we work on are lactic acid, aromatic chemicals, and single-cell protein. We also work on improving tolerance to inhibitors in lignocellulosic hydrolysates and on the co-utilization of different carbon sources.

Overview of the response of yeast cells to acetic acid stress based on CRISPRi targeting of essential genes. Figure from Mukherjee et al., 2021. We hypothesize that altering the expression of proteasomal genes can provide a means for cells that are more tolerant to oxidative stress, something we want to look into in our future research.

Cell factory design and strain development

We mainly work with yeast and filamentous fungi and routinely employ industrial strains as we want to provide solutions that could have impact also at large scale. We use both classical strain engineering (adaptive evolution and mutagenesis) and genetic engineering for converting the microorganisms into more productive, robust and inhibitor-tolerant production hosts.

CRISPR/Cas9 based genome editing and regulation of transcription

We develop genome editing and transcriptional regulation tools based on the CRISPR/Cas9-technology and synthetic transcription factors. For engineering filamentous fungi we typically use Cas9 ribonucleoparticles, which enables engineering without tool development and access to altering the genomes of novel species, speeding up strain development. For yeast we have created a CRISPRa/i toolbox that allows us to create and evaluate large amounts of strain variants.

Biosensors and high-throughput screening

We work with large strain libraries, such as CRISPRi collections that we screen under varying conditions, in high-throughput. We have developed screening methods that allow evaluating growth directly in relevant biomasses, allowing the development of cell factories for actual industrial application. Another research theme is developing and using biosensors for screening and strain development purposes.