Sunday, 12 May 2019

Genetically engineering yeast to improve understanding of how cells work

Researchers have 'fine-tuned' a major cell signalling mechanism by rewriting DNA inside yeast cells to control how they respond to their environment.

The study, which was published recently by the journal Cell, has immediate biotechnology uses but could also have wider implications for healthcare research. It is hoped being able to alter how cells react will help scientists understand how diseased cells function and lead to modified cells being used to treat patients.

Academics from the University of Cambridge and Imperial College London, in collaboration with AstraZeneca, used mathematical modelling and genome engineering to edit yeast cells to help scientists control not just what the cells sense but how they react to what they sense in a more desirable way.

Yeast was chosen because it shares key characteristics with human cells -- most importantly that it can sense its environment using G protein-coupled receptors (GPCRs).

GPCRs are receptors which enable cells to sense chemical substances such as hormones, poisons, and drugs in their environment. The cells read their environment and sense the levels of hormones such as adrenalin, serotonin, histamine and dopamine. They can also act as light, smell and flavour receptors with some located on the tongue to give us our sense of taste.

READ MORE: Yeast engineered to manufacture complex medicine

There are around 800 different GPCRs in our bodies and around half of all medication acts using these receptors -- including beta blockers, antihistamines and various kinds of psychiatric drugs. But not enough is known about how GPCR signalling works.

One of the difficulties for researchers is that DNA variations can have an impact on the signalling network and determining how parts of the DNA affect this is a major challenge.

The Cambridge team created a mathematical model of the yeast cell with varied concentrations of different cell components and found the optimum levels for the most efficient signalling of each one. This knowledge was then used to genetically modify cells by a team of researchers at Imperial College London.

Research paper:

William M. Shaw, Hitoshi Yamauchi, Jack Mead, Glen-Oliver F. Gowers, David J. Bell, David Ă–ling, Niklas Larsson, Mark Wigglesworth, Graham Ladds, Tom Ellis. Engineering a Model Cell for Rational Tuning of GPCR Signaling. Cell, 2019; DOI: 10.1016/j.cell.2019.02.023

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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