Overview
Vaccine mRNA can only work if it reaches the part of the cell where proteins are made. Can engineered protein shells protect vaccine mRNA and release it inside cells to produce an antigen, while avoiding excessive inflammation?
About this opportunity
In this PhD, you will explore an innovative approach to deliver mRNA vaccines by adapting structures found in bacteria. You will work at the interface of biology, bioengineering and medicine, designing molecular carriers for mRNA delivery and discovering how human cells respond to them.
Messenger RNA (mRNA) carries genetic information that cells can read to make proteins. In an mRNA vaccine, this genetic message enables cells to produce a viral protein that helps the immune system recognise the virus. However, mRNA is fragile. It needs a protective carrier to enter cells and must then be released so that its genetic information can be read.
Our research team has established how to build tiny, hollow protein shells outside living cells. Inspired by natural bacterial compartments called carboxysomes, they can be redesigned to carry different molecules. Your challenge will be to turn them into packages that protect vaccine instructions during delivery and open when needed.
What will you discover?
You will first investigate how to perform in vitro assembly of shells and recruit mRNA into the shells. Using powerful microscopes and laboratory tests, you will examine the packages and find out how well they protect their contents.
Next, you will explore how to make the shells open after entering a cell. Some compartments inside cells are mildly acidic. This change in acidity could act as a signal for the shell to open and release mRNA. You will also investigate how the mRNA can escape these compartments and reach the machinery that reads its instructions. An easily detected protein will provide a clear sign that delivery has worked.
Finally, you will test the strategies for making an influenza protein and examine how human cells respond. You will compare the protein shells with lipid nanoparticles used in many mRNA delivery systems, assessing protein production, cell health and immune responses. The results from laboratory-grown cells, including donated human immune cells, will guide future research programme to validate the efficacy of the protein nanocage-based mRNA delivery system.
What will you gain?
At the University of Liverpool, you will work in the laboratories of Professors Luning Liu and Neill Liptrott, combining expertise in building protein structures with understanding how delivery materials interact with the immune system. You will learn to design proteins, work with RNA and human cells, use advanced microscopes, and analyse your results.
Curiosity, careful thinking and enthusiasm for working across disciplines will help you grow into an independent researcher. The discoveries could lay the groundwork for a delivery platform that can be adapted to different vaccines and help answer a compelling question: How can we design next-generation mRNA vaccines with programmable carriers that protect mRNA and release it efficiently inside cells while minimising unwanted inflammation?