Engineering Neofunctionalization in a Model Triterpene Synthase (HEMMINGS_U17DTP1)

Lead Research Organisation: University of East Anglia
Department Name: Graduate Office

Abstract

Enzyme engineering plays a major role in the UK bioeconomy as a route to the discovery of novel compounds and the production of high-value chemicals. The global market for industrial enzymes is predicted to reach $7bn by 2018.

Plant-derived natural products form a large set of compounds frequently found to have pharmaceutical, agricultural and industrial biotechnology applications yet their commercial exploitation is often limited by their synthetic intractability. In a collaboration between the groups of Dr. Andrew Hemmings (University of East Anglia) and Professor Anne Osbourn (John Innes Centre) a major project is underway to develop engineered natural product biosynthetic enzymes capable of producing novel, exploitable compounds

A PhD research studentship has become available to carry out exciting research aimed at reengineering a critical triterpene biosynthetic enzyme. The successful candidate will play a central role in attempts to engineer the catalytic properties of this target. To achieve this they will receive training in cutting edge methods of protein engineering, molecular and structural biology, analytical biochemistry and computational modelling. The research will make extensive use of local facilities at UEA including the Centre for Structural and Molecular Biochemistry (CMSB) and at the John Innes Centre.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011216/1 01/10/2015 30/09/2023
1937543 Studentship BB/M011216/1 01/10/2017 30/09/2021 Hans Emile Pfalzgraf
 
Description "Design and build an enzyme" activity stand at the Norwich Science Festival 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I designed and ran an activity stand for the Norwich Science Festival. I told the story of a farmer, and related it to my project, to hundreds of people, mostly young children and their parents. The biosynthesis that my project focuses on was explained using toy-bricks. The participants were then challenged to engineer their own toy-brick enzymes to allow it to form a given new toy-brick molecule. We designed small lanyard cards to take home that explain our research and give a further activity explaining enzyme engineering. All 600 of these were taken by the attendants.
I discussed science with many enthusiastic children in the hope they would carry on the science path.
Year(s) Of Engagement Activity 2018
URL https://norwichsciencefestival.co.uk/events/chemistry-day/
 
Description "Engineer your own enzymes" activity stand at the Norwich Science Festival 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I designed an activity stand for the Norwich Science Festival which I ran with four other postgraduate students. We told the story of a farmer and related it to my project. Hundreds of people, mostly young children and their parents, found the fluorescence of oat seedling roots caused by avenacin and learned the mechanism of action. Its biosynthesis by enzymes was explained using toy-bricks. The participants were then challenged to engineer their own toy-brick enzymes to allow it to form a given new toy-brick molecule. We designed small lanyard cards to take home that explain our research and give a further activity explaining enzyme engineering. Several hundreds of these were taken home by the attendants.
The stand enabled discussions between parents and scientists, for example about GMOs and gene editing.
Year(s) Of Engagement Activity 2019
URL https://norwichsciencefestival.co.uk/events/molecular-materials-chemistry-day/
 
Description Explaining my research to year 9 pupils 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact As part of a bigger outreach event and activity, I briefly explained what my research of enzyme engineering was to two different groups of 20 Year 9 pupils from regional schools that have low university participation.
Year(s) Of Engagement Activity 2020
 
Description Falling Walls Lab Surrey competition 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact A 3-minute TED-talk style presentation on our research was given to a diverse audience (eg entrepreneurs, academics, students and the mayor of Guildford) as part of a competition to promote the best ideas and presenters. An investor asked for further information at the following networking event.
Year(s) Of Engagement Activity 2018
 
Description Play-testing a board game on enzyme engineering 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact I designed a fun board game that use toy-bricks to explain how an enzyme recognises a substrate through complementary of shape and through the local chemical nature. The game makes both players engineer the enzyme to fit a new substrate. This was play-tested with other local postgraduate students from a range of fields. This will then be improved to be run with the general public at science festivals, game festivals and outreach opportunities.
Year(s) Of Engagement Activity 2020
 
Description Presenting my research at the Molecular Microbiology seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact I presented my research in 30 min at an open seminar and got a few questions and suggestions from an audience of academics and students.
Year(s) Of Engagement Activity 2019
 
Description Presenting our video production pipeline and pilot to BecA-ILRI in Nairobi for our PIPS 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact The output of my PIPS placement was a video production pipeline for BecA-ILRI, Nairobi, as well as a pilot episode for the series "Enabling Science", which aims to teach soft skills to scientists for free on YouTube, mainly aimed at low- and middle-income countries. The scientists present said they were very impressed by our good work and the series can now be taken over by the next PIPS students or anyone else who can get funding for it.
Year(s) Of Engagement Activity 2019
URL https://youtu.be/W9es-LFba7g
 
Description Publicity video about enzymes for the Norwich Science Festival 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A video advertising my talk on enzymes at the Norwich Science Festival was recorded and edited professionally, then posted on the official Facebook page of my university. It has been seen almost 3,000 times and many of my friends stumbled upon it.
Year(s) Of Engagement Activity 2018
URL https://www.facebook.com/ueaofficial/videos/325742221313462/
 
Description Speak Up for Food Security qualifiers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact During a storytelling masterclass organised by Global Food Security, I delivered an emotional presentation which explained my research and its importance, as well as the impacts of GM policies on related science and its applications. It exposed the paradox of GM and gene editing vs radiation breeding to an audience GFS employees and of postgraduate students and post-docs working in a wide variety of fields all over the UK.
Year(s) Of Engagement Activity 2020
URL https://www.foodsecurity.ac.uk/activities/speakup/#post-16143
 
Description Summer school lecture to Y10 students 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact As part of a lecture about university and biochemistry, I explained my research to a class of summer school year 10 students. The aim of the lecture was to get the students enthused about biochemistry, show them that scientists are normal humans with hobbies and convince them that there are many different skills they can capitalise on to succeed at university.
Year(s) Of Engagement Activity 2018
 
Description UEA Open Day July 6th 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Prospective students were introduced to biochemistry through the lens of the kind of problems our research is trying to solve, so they could make an informed decision about choosing a biochemistry degree. Through explanations and activities, I covered topics such as protein structure, directed evolution and rational enzyme engineering. It sparked an interest in biochemistry in some attendants that were originally looking at other degrees. Some attendants have chosen to study biochemistry.
Year(s) Of Engagement Activity 2019
 
Description UEA Open Day October 21st 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Prospective students were introduced to biochemistry through the lens of the kind of problems our research is trying to solve, so they could make an informed decision about choosing a biochemistry degree. Through explanations and activities, I covered topics such as protein structure, directed evolution, rational enzyme engineering and enzyme assays. Some of the attendants went on to study a Biochemistry degree.
Year(s) Of Engagement Activity 2017
 
Description UEA Open day October 19th 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Prospective students were introduced to biochemistry through the lens of the kind of problems our research is trying to solve, so they could make an informed decision about choosing a biochemistry degree. Through explanations an activities, I covered topics such as protein structure, directed evolution and rational enzyme engineering. Some of the attendants were not originally interested in biochemistry but found it cool. Some attendants have chosen to study biochemistry.
Year(s) Of Engagement Activity 2019