Our projects
In the Knott Lab, we offer a diverse range of projects for students, staff and post-doctoral researchers to contribute great scientific breakthrough medical research. Our projects have both significant impact in basic research and translational application.
Understanding Cas13 mechanisms
Cas13 formerly known as C2c2 is a Class 2 type VI CRISPR system. Upon activation the protein cuts single stranded RNA (ssRNA) through its nuclease domain (HEPN). We seek to uncover the molecular mechanism of the HEPN domain in hopes to improve RNA targeting capabilities of this protein for diagnostics and precise RNA targeting.
The success of this project will change the landscape of CRISPR research and allow us to probe deeper in understanding how other CRISPR system functions.
Roland, PhD student
Reshaping vaccine production
Despite the successes achieved with T7 RNA polymerase, we recognise the need for improvements in efficiency, scalability, and adaptability for both research and commercial production of mRNA vaccines. Our research is dedicated to harnessing the evolved diversity of novel phage RNA polymerases to expand the repertoire of enzymes with enhanced properties.
The success of this project has the potential to accelerate the development and deployment of mRNA vaccines for a wide range of diseases, paving the way for more efficient, scalable, and accessible vaccine solutions.
Jenni, Post-doctoral researcher
Developing CRISPR diagnostics
In rural areas where access to sophisticated laboratory facilities is limited, rapid and reliable diagnostics are crucial for timely disease management. CRISPR offers a highly specific and sensitive detection platform, making it an ideal candidate for point-of-care applications. Unlike conventional PCR, which often requires complex equipment and skilled personnel, CRISPR-based diagnostics can be implemented with simpler instrumentation, enabling deployment in resource-limited settings.
By harnessing the programmable nature of CRISPR, we can design these diagnostics to target specific viral sequences, ensuring both sensitivity and specificity in pathogen detection.
Nathan, Research officer
CRISPR engineering & evolution
Despite CRISPR systems found in nature having a diverse range of function and substrates, we are yet to find examples of systems which display many of the behaviours required for the next generation of CRISPR biotechnologies. To address these apparent holes within the “CRISPRverse” we are supplementing our metagenomics program with protein engineering and directed evolution approaches probing the fitness landscape beyond that found in nature.
By designing and evolving bespoke Cas sensors and effectors we will expand the tools available and accelerate research in the second decade of CRISPR biotech
Loki, PhD student
A little help from AI
The development of AI enables us to not only predict but also design novel nucleic acid binding proteins whilst gaining deeper insights into their structural nuances and functional characteristics.
The successful realization of this project holds immense promise for creating tailored biomolecules with applications ranging from synthetic biology to therapeutic interventions. By leveraging the power of computational biology, we aim to unlock the full potential of nucleic acid binding proteins, opening up avenues for groundbreaking discoveries and technological advancements in the life sciences.
Cyntia, Post-doctoral researcher
Enigmatic proteins
At the nexus of the prokaryotic and eukaryotic worlds lie the enigmatic and understudied Archaea. These microorganisms are often found in extreme environments, and as such remain under sampled and their genomes and novel proteins under characterised. The recent description of huge extrachromosomal elements (called Borgs) associated with Archaea expand the realms of the unknown, with up to 15% of the ORFs identified having no known homology to existing proteins.
This project aims to decipher the function and role of many of these proteins within the Archaeal and Borg genomes, with a specific focus on identifying novel nucleic acid binding proteins, nucleic acid modifying enzymes, and nucleic acid sensors.
Rebecca, Lab manager
Novel microbial defence systems
The Knott Lab’s expertise in molecular biology, biochemistry and structural biology is also applied to characterising bacteria ldefence systems beyond CRISPR-Cas. Million of years of host-pathogen co-evolution between microbes and their viruses has resulted in an incredible diversification of attack and defence system encoded into genomes. In recent years, the systematic exploration of metagenomes unveiled a widespread, growing, and uncharted repertoire of novel defence systems that microbes employ to fend off bacteriophages
Given their biological importance and potential as biotech tools, we aim to identify and thoroughly characterise novel microbial defence systems with the goal of distilling new biotech tools as well as charting this ancient arms race.
Giovanni, PhD student