Biodesign and engineering of functionalized spider silk variants

Spider silk is a high-performance biomaterial with exciting applications ranging from personal protective clothing to surface coatings for medical implants and guides for neuronal regeneration. Harvesting silk from spiders is tedious and economically not viable on a large scale. Consequently, the heterologous production of silk in a wide range of host organisms (from bacteria to goats) has been the focus of intense synthetic biology research. In this project, we intend to build on these advances to create libraries of functionalised spider silk derivatives for various applications.

Design: The first part of the project will exploit recently available spider genome and transcriptome sequences to characterize the full spectrum of natural spider silk sequence motifs. The aim is to identify design patterns of silk sequences that correlate with biophysical properties of the resulting silk.

Build: The second part of the project will test the inferred design patterns, using DNA synthesis and automated DNA assembly pipelines to create diverse libraries of silk proteins, for expression and characterization. We will use Escherichia coli, as well as biotechnologically promising alternative host species, to produce and isolate the engineered silk proteins.
Test: To facilitate the high-throughput testing of these libraries, a third part of the project will focus on the development of suitable tags for the expressed silks, which will allow rapid determination of expression levels and correlation with key properties of the resulting spun material using a collection of biophysical and materials sciences assays.

Learn: The fourth part of the project uses machine learning methods to predict improved sequence designs, which will be tested in several iterations of the design cycle.
This project provides comprehensive interdisciplinary training in methods pioneered by the supervisory team, across a range of key disciplines at the interface of biology and engineering, essential for the next generation of biotechnology scientists.

The 2016 UK Roadmap Bio-design for the Bio-economy highlighted the substantial impact that synthetic biology can bring to the UK and global economies by developing: frontier science and technology; establishing a healthy innovation pipeline; a highly skilled workforce and an environment in which innovative science and businesses can thrive. Synthetic biology promises to transform the UK Bio-economy landscape, bringing bio-sustainable and affordable manufacturing routes to all industrial sectors and will ensure society can tackle many contemporary global Grand Challenges including: Sustainable Manufacturing, Environmental Sustainability Energy, Global Healthcare, and Urban Development. Whilst synthetic biology is burgeoning in the UK, we now need to build on the investments made and take a further lead in training next generation scientists to ensure sustained growth of a capable workforce to underpin the science base development and growth in an advanced UK bio-economy.
This training provided by this CDT will give students from diverse backgrounds a unique synthesis of computational, biomolecular and cellular engineering skills, a peer-to-peer and industrial network, and unique entrepreneurial insight. In so doing, it will address key EPSRC priority areas and Bioeconomy strategic priorities including: Next-generation therapeutics; Engineered biomaterials; Renewable alternatives for fuels, chemicals and other small molecules; Reliable, predictable, and scalable bioprocesses; Sustainable future; Lifelong health & wellbeing.
Advances created by our BioDesign Engineering approach will address major societal challenges by delivering new routes for chemical/pharma/materials manufacture through to sustainable energy, whilst providing clean growth and reductions in energy use, greenhouse gas emissions and carbon footprints. Increased industry awareness of bio-options with better civic understanding will drive end-user demand to create market pull for products. The CDT benefits from unrivalled existing academic-industry frameworks at the host institutions, which will provide direct links to industrial partners and a direct pathway to early economic and industrial impact.

This CDT will develop 80-100 next-generation scientists and technologists (via the funded cohort and wider integration of aligned students at the three institutions) as adept scientists and engineers, instilled with technical leadership, who as broadly trained individuals will fill key skills gaps and could be expected to impact internationally through leadership roles in the medium term. Importantly the CDT addresses key skill-gaps identified with industry, which are urgently required to create and support high value jobs that will enable the UK to compete in global markets. Commercialisation and entrepreneurship training will equip the next generation of visionaries and leaders needed to accelerate and support the creation of new innovative companies to exploit these new technologies and opportunities.

The UK government identified Synthetic Biology as one of the "Eight Great Technologies" that could be a key enabler to economic and societal development. This CDT will be at the forefront of research that will accelerate the clean growth agenda and the development of a resilient circular bioeconomy, and will align with key EPSRC prosperity outcomes including a productive, healthy and resilient nation. To foster wider societal impact, the CDT will expect all students to contribute to public outreach and engagement activities including: open days, schools visits, and science festival events: students will participate in an outreach programme, with special focus on widening participation.

This CDT will contribute to the development of industrial strategy through the Synthetic Biology Leadership Council (SBLC), Industrial Biotechnology Leadership Forum (IBLF), and wider Networks in Industrial Biotechnology and Bioenergy and Professional Institutes.