The evolution of multiple active site configurations in a designed enzyme – New Nature Communications Paper!

 

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Congratulations to Nansook and everyone involved in this project! This has been a great collaboration with Lynn Kamerlin (Uppsala University), Chris Easton (ANU) and Michelle Coote’s (ANU) groups.

In this work, we follow changes in conformational sampling, electrostatic preorganization, and quantum tunneling along the evolutionary trajectory of a designed Kemp eliminase. We observe that in the Kemp Eliminase KE07, instability of the designed active site leads to the emergence of two additional active site configurations. Evolutionary conformational selection then gradually stabilizes the most efficient configuration, leading to an improved enzyme. This work exemplifies the link between conformational plasticity and evolvability and demonstrates that residues remote from the active sites of enzymes play crucial roles in controlling and shaping the active site for efficient catalysis.

https://www.nature.com/articles/s41467-018-06305-y

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Postdoctoral Fellow Position in the Jackson Lab – Apply Now!

Come and work with us on an exciting, collaborative project at the Australian National University!

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The ANU Grand Challenge Research Program on Novel Miniaturized Medical Sensor Technology is now advertising Postdoctoral Fellow / Research Fellow positions located each in the Research Schools of Chemistry, Engineering, and Physics to work on the development of novel miniaturized biomedical sensors that can be integrated into wearable and point-of-care devices. These positions will work synergistically with the ANU Grand Challenge team benefitting from the breadth of the research programs and expertise. This project aims to revolutionise personalised medicine by providing new means for non-invasive collection and analysis of health data including the development of miniaturized sensors for detection of biomarkers in multiple sclerosis and diabetes.

The Research School of Chemistry Research Fellow will work in Associate Professor Colin Jackson’s group, and be responsible for design, engineering, and production of proteins as a key component of these biosensors. This could include engineering binding selectivity, optimizing ligand affinity, and chemical modification of the protein to function as part of a complex matrix, such as protein hydrogels.

For more details on how to apply, please follow this link: http://jobs.anu.edu.au/cw/en/job/526630/postdoctoral-fellow

 

 

Galen hits ‘Submit’ on his PhD Thesis!

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Congratulations to Galen Correy who submitted his PhD thesis last week! Here he is clicking on the ‘submit’ button. Well done Galen!

 

Check out a few of Galen’s papers:

 

 

 

 

Ben Clifton awarded ‘Best Thesis’

Ex-Jackson group member Dr. Ben Clifton has been awarded the ‘ANU Research School of Chemistry Director’s award for the Best Thesis 2017’. Ben’s PhD thesis ‘Functional evolution of solute-binding proteins’ describes the use of ancestral protein reconstruction to explore the molecular evolution of binding specificity and catalysis in amino-acid binding proteins.

You can find some of Ben’s published work here:

 

Congratulations Ben!

New Nature Chemical Biology paper!

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Image result for Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS

 

Link to paper

The amino acid glycine is an important inhibitory neurotransmitter and co-agonist of the N-methyl-D-aspartate receptors involved in synaptic plasticity. In this work, published in Nature Chemical Biology, we describe the computational design, development, and application of the first optical sensor for glycine. This FRET sensor can be used with single and two-photon excitation fluorescence microscopy. Here, we show that it can be used in combination with electrophysiology to investigate the spatial distribution of glycine in the extracellular space, and to probe how glycine concentrations change in response to plasticity-inducing stimuli.

This work was done in collaboration with Christian Henneberger’s group (University of Bonn, Institute of Cellular Neurosciences). Congratulations to Will, Michel and everyone involved in this work.