Unlock the Future: Engineering Biology to Sense the Impossible

Secondary Supervisor(s): TBC

University of Registration: University of Birmingham

BBSRC Research Themes: Integrated Understanding of Health (Pharmaceuticals)

Project Outline

Join the Revolution: PhD in Engineering Biology to Unleash the Power of Nature's Sensing Abilities!

The Challenge

What if we could harness the incredible natural powers that animals and organisms use to sense the world around them? Imagine a world where we can detect everything from hormones like insulin, to plant diseases, to narcotics—all without relying on animals. This is your chance to join the cutting edge of Engineering Biology, where science and nature collide to create extraordinary, life-changing sensors.

At the frontier of synthetic biology, we're developing revolutionary sensors inspired by nature’s finest mechanisms, like the cellular receptors in organisms that detect chemical signals. Picture sensors that could revolutionize healthcare, agriculture, and defense, pushing the boundaries of what's possible!

Your Mission

You'll be at the forefront of this breakthrough by working on a "bottom-up" approach, combining biological components like proteins and receptors to build a next-gen sensing system. Our lab has already made global strides with methods such as SMALPs, which stabilize key proteins (like GPCRs), opening the door to new sensing platforms that could change industries.

We're not just theorizing—we’re working with sectors ranging from agriculture to defense, creating real-world solutions that these fields are eagerly awaiting. If you’re excited by the chance to challenge scientific conventions and see your work applied in the real world, this PhD is your chance to make an impact.

Scientific Background

Our breakthrough technique, developed in 2009, SMALPs (Styrene-Maleic Acid Lipid Particles) (1), allows us to stabilize membrane proteins—nature's ultimate sensor molecules—while maintaining their natural environment. This technology enables the creation of highly stable and active proteins, including GPCRs, which act as nature’s "detectors" for everything from hormones to neurotransmitters (2,3).

We’re now aiming to take this pioneering work even further, using GPCR-SMALPs to develop a completely new class of molecular detectors. These could be applied across medicine, agriculture, and even the detection of substances like cannabis. We’ve already developed a method to track the shape changes these proteins undergo, using fluorescence detection, and are now exploring even more detection modalities.

Work in This Project As a PhD student in our lab, you’ll continue the exciting work already laid by a fellow PhD researchers, who has developed a system to produce a range of GPCR-SMALPs. You’ll take these advancements and push them even further, exploring cutting-edge detection methods like fluorescence and electrochemical detection.

Your goal will be to build a platform capable of creating the next generation of molecular detectors, applying your research to real-world problems, with a focus on global impact.

Are you ready to be a part of this scientific revolution? Apply now to embark on this exciting journey and help shape the future of sensor technology.

References

1) Knowles, T.J., et al., J Am Chem Soc, 2009. 131(22): p. 7484-5.

2) Grime R.L. et al., Nanoscale. 2021 Aug 21;13(31):13519-13528.

3) Routledge S. J. et al., Biochim Biophys Acta Biomembr. 2020 Jun 1; 1862(6):183235.

Comparative antibody discovery strategies for transmembrane proteins utilising styrene maleic acid lipoproteins (SMALPs) and soluble extracellular domains powered by next generation sequencing analysis

Secondary Supervisor(s): Dr Tim Knowles

University of Registration: University of Birmingham

BBSRC Research Themes: Integrated Understanding of Health (Pharmaceuticals, Regenerative Biology)

Project Outline

Chimeric antigen receptor (CAR)-T cells and bispecific T-cell engagers (BiTes) are opening new treatment paradigms for many oncology diseases by priming the immune system to attack cancer cells.

Such therapies have been built using the modular building blocks of specific antibody domains targeting the extracellular domains of membrane bound proteins. The extracellular domains used for discovery are soluble versions produced recombinantly. This omits key epitopes close to membrane which may afford both BiTes and CAR-T cell greater efficacy by creating a tighter immune synapse which in turn drives efficacy of the therapy.

One way of improving this would be to use whole membrane proteins in the process. However generating whole membrane proteins in an active stable form has been historically challenging. In Birmingham a novel method, Styrene Maleic Lipid Particles or SMALPs has been developed which provides a simple novel way of solubilising the whole membrane protein which may give access to membrane proximal domains for discovery workflows.

This project aims to use SMALPs to enhance therapeutic development and use avante garde data analysis coupled with comparative analysis of sequencing outputs to enhance to development of successful new therapies.

Aims

This project aims to determine:

1. Does using SMALPs as an antigen for antibody discovery improve the outputs compared to extracellular domains alone?

2. Can the chemistry of the polymer used for solubilising the transmembrane protein be altered to improve discovery workflows?

3. Can data be analysed to determine the binder differences? Do these different binders afford greater tumour killing efficacy?

4. (Stretch aim) Can these different binders be the starting point for machine learning based diversification to improve killing efficacy?