The main theme of my laboratory is to detect and correct "bad behaviour" in cells using a combination of in vivo biosensors and synthetic biology.
*Not a scientist? See below for the Plain English version of this webpage.*
What are in vivo biosensors? Most classical biosensors (like those used in blood sugar monitoring) rely on electrochemistry to convert the concentration of a molecule of interest into a digital display. However, there are a whole class of biosensors that are entirely genetically-encoded either by fusing a transcriptional element that detects the molecule of interest to a reporter protein like GFP or through proteins that have the ability to sense the molecule and convert the concentration into an output. These genetically-encoded sensors are convenient tools for monitoring what is going on inside living cells since they don't require the addition of exogenous reagents or abiotic elements. We use sensors like these to monitor cellular behaviour under different conditions. They can be used in conjunction with external stimuli (e.g. changing medium cells are fed) to control cellular behaviour.
What is synthetic biology? Synthetic biology is an engineering approach to biology which attempts biological redesign from a set of standard, well-characterised "parts" (genetic elements like promoter sequences and ribosome binding sites). Synthetic biology is a powerful tool to exploit the vast biological knowledge that has been accumulating since the advent of recombinant DNA technology. We use synthetic biology to design new circuits to control cellular behaviour. These circuits can be linked to the biosensor output from above in order to create a self-correction system within an organism of interest.
- Biopharmaceutical processing
- Neurodegeneration and ageing
- Tools for synthetic biology
Plain English version:
Since the 1970's, scientists have had the ability to change the genes of an organism-- in fact, we've gotten pretty good at doing so! This allows us to make organisms do work for our benefit- from making medications to manufacturing materials for us.
Work in my laboratory has two goals. First, we try to develop proteins that can give us a window to what is going onside in an organism by turning colours to warn us when things have gone wrong inside the cell. Second, based on that coloured signal, we try to add genes to the organism that help us correct the problem. Our ultimate goal is to develop self-correcting organisms.
Keck FD, Polizzi KM, 2020, Microbial interventions are an easier alternative to engineer higher organisms., Microb Biotechnol
et al., High resolution biosensor to test the capping level and integrity of mRNAs, Nucleic Acids Research, ISSN:0305-1048
Keck FD, Polizzi K, Microbial interventions as alternatives to eukaryotic engineering, Microbial Biotechnology, ISSN:1751-7907
Aw R, Spice AJ, Polizzi K, Methods for expression of recombinant proteins using a Pichia pastoris cell-free system, Current Protocols in Protein Science / Editorial Board, John E. Coligan ... [et Al.], ISSN:1934-3655
et al., 2020, Improving the reaction mix of a Pichia pastoris cell-free system using a design of experiments approach to minimise experimental effort, Synthetic and Systems Biotechnology, Vol:5, ISSN:2405-805X, Pages:137-144