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.
et al., Computational re-design of synthetic genetic oscillators for independent amplitude and frequency modulation, Cell Systems, ISSN:2405-4712
et al., 2018, Exploring cellular behavior under transient gene expression and its impact on mAb productivity and Fc-glycosylation, Biotechnology and Bioengineering, Vol:115, ISSN:0006-3592, Pages:512-518
et al., 2018, Investigating the consequences of asymmetric endoplasmic reticulum inheritance in Saccharomyces cerevisiae under stress using a combination of single cell measurements and mathematical modelling, Synthetic and Systems Biotechnology, ISSN:2405-805X
Anastasiadi M, Polizzi K, Lambert RJW, 2018, An improved model for the analysis of combined antimicrobials: a replacement for the Chou-Talalay combination index method, Journal of Applied Microbiology, Vol:124, ISSN:1364-5072, Pages:97-107
et al., 2017, Model-based investigation of intracellular processes determining antibody Fc-glycosylation under mild hypothermia, Biotechnology and Bioengineering, Vol:114, ISSN:0006-3592, Pages:1570-1582