Investigating the molecular basis for vitamin B12 transport between bacteria and algae

Lead Research Organisation: University of Cambridge
Department Name: Plant Sciences

Abstract

Vitamin B12 is a water-soluble co-factor that is produced by prokaryotic organisms. Fifty percent of algal species are dependent on vitamin B12 for growth, thus they must obtain sufficient quantities of the vitamin from their environment. In doing so, algae may interact with bacteria and form symbiotic relationships with them. The aim of this project is to investigate the proteins and regulatory mechanisms involved in vitamin B12 transport in bacteria and algae, making use of Chlamydomonas reinhardtii and Mesorhizobium loti which are partners of a model algal-bacterial symbiotic system that is regulated by vitamin B12 and photosynthate exchange.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011194/1 30/09/2015 31/03/2024
1644238 Studentship BB/M011194/1 30/09/2015 29/09/2019 Andrew Sayer
 
Description A protein (CrCBA1) was identified in the green alga Chlamydomonas reinhardtii that is necessary for vitamin B12 acquisition. This is important as over half of algal species require vitamin B12 for growth, therefore, this process is central to the ability of algae to grow.

Diverse algal species were found to have this protein, and it was also found in environmental samples. This protein was much more common than previously thought, which suggests it is commonly used for vitamin B12 acquisition in algae. This also helped identify high conserved regions of the protein, which indicate regions that are functionally important.

An RNA sequencing experiment was performed that helped to identify new genes that change in expression due to the presence/absence of vitamin B12. Additionally, genes were identified that are co-expressed with CrCBA1.

A number of additional genes were identified by computational methods, that might be important for vitamin B12 acquisition. This is a resource that could be further investigated in future research.
Exploitation Route Vitamin B12 acquisition is a process essential for the growth of over half of algal species. Therefore, this research has environmental implications. Further research could focus on understanding the wider regulatory network that is associated with vitamin B12 acquisition. This could be achieved by making use of strains generated in this research to identify CrCBA1-protein interactions.

Most algae associated with harmful algal blooms are dependent on vitamin B12 for growth, therefore, the increased understanding of vitamin B12 acquisition in algae (from this research) could be used to help understand and control this process.

Algae are used for biotechnological purposes and grown at scale. The understanding that a protein similar to CrCBA1 is needed for vitamin B12 uptake could be used to help design more stable cultures during bioproduction.
Sectors Agriculture

Food and Drink

Environment

Manufacturing

including Industrial Biotechology

URL https://doi.org/10.17863/CAM.49830
 
Description 18-BBSRC-NSF/BIO Focusing a quantitative lens on synthetic phototrophic communities
Amount £600,178 (GBP)
Funding ID BB/T010525/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2020 
End 09/2023
 
Description Enhancing cobalamin (vitamin B12) bioavailability in culturally appropriate foods in India
Amount £1,600,000 (GBP)
Funding ID BB/S014020/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 03/2019 
End 02/2021
 
Description Frank Smart Studentship
Amount £2,000 (GBP)
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom
Start 11/2018 
End 11/2018
 
Title RNA sequencing dataset of vitamin B12 acquisition impaired line and response to vitamin B12 
Description Dataset of Chlamydomonas reinhardtii lines (parental line, and vitamin B12 uptake impaired line) with and without vitamin B12. This provides information about vitamin B12 responsive genes, and which genes are associated with vitamin B12 uptake function. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? No  
Impact Identified new genes that may be responsive to vitamin B12. Identified new genes that may be associated with vitamin B12 acquisition. 
 
Title Strains where vitamin B12 uptake can be regulated by presence/absence of thiamine 
Description An algal strain was generated that would not acquire vitamin B12 in the presence of thiamine. This strain can be used in the future to further investigate vitamin B12 metabolism. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? No  
Impact Confirmation that CrCBA1 is necessary for vitamin B12 acquisition in Chlamydomonas reinhardtii. 
 
Description Systems biology of hot spring microbial mats 
Organisation Carnegie Institution for Science (CIS)
Country United States 
Sector Charity/Non Profit 
PI Contribution Bioinformatics pipeline to explore role of vitamin exchange in initiating and maintaining microbial communities
Collaborator Contribution Expertise in identification, isolation and characterisation of microbial communities
Impact A joint NSF/BBSRC grant
Start Year 2019
 
Description Agritech East - outreach evening to algal innovation centre by those interested in and working in farming sector 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact This is the text from the Agritech East Report after the event:
Sainsbury Lab and Algal Innovation Centre - Cambridge University

At the end of January we hosted a Young Innovators' Forum (YIF) visit to the Sainsbury Lab and Algal Innovation Centre, Cambridge University. This was visit as part of YIF programme which aims to bring together early career entrants from across farming, science and technology at innovative agri-business and research facilities.

On the night we were joined by farmers, scientists, researchers and engineers who were all interested to find out about the work happening in the lab. The Sainsbury Lab is a world class research facility which opened in 2011. The group found out that the research which is carried out is exploring the regulatory systems which control growth and development in plants. We were able to get an insight into the labs as we walked through the building due to the open plan nature of the space. Unlike some research facilities, the Sainsbury Lab is unusual in having individuals from different research groups sat on the same benches, which encourages more conversation and collaboration across different research strands. We heard about the findings of some of the research and particularly enjoyed finding out about the most unusual discovery which was made totally by accident when a plant was found to produce minerals that were previously only believed to be found in asteroids!

We then moved onto the Algal Innovation Centre which sits within the Botanic Gardens. A purpose built facility, the AIC provides a secure environment to carry out research into the uses and behaviour of algae. Matt Davey, Senior Research Associate, talked us through some of the different work which has been carried out within the lab. This includes working with a local water company on growing algae on waste nitrate which can then be used to produce energy by putting it into an anaerobic digester. We learnt about other research linked to the health food sector due to the fact that Omega oils, which in the past have been extracted from fish, an actually be captured from the algae which produces it. Some of the work that Matt and his team have been carrying out is how to optimise growing conditions and nutrient supply, especially understanding how different algal strains survive in different climates. It was a surprise to learn that algal pigments can be found in everyday products such as Smarties and wine gums!

Finally, we were shown around the Plant Growth Facility. In this building there are lots of separate chambers in which all factors needed for plant growth can be controlled, such as humidity and light. This enables researchers to be able to drill down into the specific variables that might influence or affect a particular result. As we walked around the facility, we saw a range of plant species being tested on including wheat, potatoes and rice. These secure, air tight chambers also allow tests into plant pathogens to happen as they can be contained and assessed within a rigorous framework.

We were really lucky to be able to explore the Sainsbury Lab and Algal Innovation Centre. It was so interesting to hear about all the research that is going on which could impact the agricultural industry in the future.

As with all of our YIF events, attendees then had the opportunity to discuss the tours as well as talk about their experience and knowledge in the area. We chatted to some of the attendees to see what they got from attending the event, here is what they had to say:

Matt White, Engineer, Cambridge Consultants

The YIF visit was an excellent opportunity for industry members like ourselves to learn about the cutting-edge research being carried out in agricultural sectors. Having the opportunity to speak with leading researchers in algae growth and cultivation was fascinating and highly valuable for expanding our knowledge in this area! These events are great at increasing links between academia and industry to help us develop agricultural technology together more effectively.

Pamela Ribone, Researcher, Sainsbury Lab

The reason for attending the YIF visit was that I really wanted to try and apply what I have done so far with my research to a more applied science, and this was an incredible opportunity to know more about what is in between really basic science and the final application to a product. The Algal Innovation Centre looks like the kind of things I would like to go for the next step. From the visit I understood that they do laboratory research, but focusing on solving problems.
Year(s) Of Engagement Activity 2020
URL https://www.agri-tech-e.co.uk/wp-content/plugins/civicrm/civicrm/extern/url.php?u=23903&qid=1491603
 
Description Contribution to The Food Programme on algal foods 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact The Food Programme on BBC Radio 4 considered the potential of using microalgae as a general foodstuff (for protein, lipids and nutrients such as vitamins). My contribution was reported in the newspapers (eg Daily Telegraph) and widely on social media. I was subsequently interviewed by 15-20 BBC local radio stations about what microalgae were and how they might be grown for food and nutritional supplements in a sustainable way. The interest in this topic has continued with several other media interviews showing an appreciation of the advantages of using microalgae as food.
Year(s) Of Engagement Activity 2020
URL https://www.bbc.co.uk/programmes/m000cyvk
 
Description Festival of Plants 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Departmental outreach event where members of the public find out what research is being conducted in the department. Our group focussed on providing knowledge and information about algae and their uses in industrial processes and the food sector.
Year(s) Of Engagement Activity 2018,2019
 
Description Future Foods Symposium, MPI Molecular Plant Physiology, Golm Germany 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I present on 'Algae for Food - enhancing nutritional value and reducing waste' explaining how microalgae have potential as a protein feedstock, with a high vitamin content, and how their cultivation might also be combined with valorising waste streams. Several of the mainly postgraduate student audience contacted me subsequently to discuss options for future study or scholarships in this area, and two of the companies there want to explore possibilities for collaboration/consultation about how to grow microalgae
Year(s) Of Engagement Activity 2019
URL https://plants-and-people.mpg.de/
 
Description SRA Payam Mehrshahi and Dr Lorraine Archer presented via a video walk-through the Algal Innovation Centre for the EIT food workshop ALGAL BIOTECHNOLOGY 2020 - TECHNIQUES AND OPPORTUNITIES FOR THE SUSTAINABLE BIOECONOMY 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Due to Covid-19 restrictions the EIT Food Professional Development course was redesigned so that 3x 2day courses were combined and presented online once over a two-day course. As the lead organisation, the University of Cambridge team (Payam Mehrshahi, Matthew Davey, Lorraine Archer) produced daily programme of lecture/seminars that brought together leading international experts to introduce the theory of techniques, SOPs best practice and live demonstration of equipment and facilities. The course offered insights and examples from an industrial and entrepreneurial perspective, that helped the participants to start or improve their own algal-based business.
The video walk-through of the Algal Innovation Centre at the University of Cambridge was designed by Payam and Lorraine to reflect the wide range of research involving algae that is carried out in the university and in this facility. The 30 minute video was followed by a 45 minute Q&A session during which participants asked about technical aspects of equipment, consumables, algae strains, culturing conditions and trouble shooting advice.
Year(s) Of Engagement Activity 2020
URL https://www.eitfood.eu/media/documents/ALGAL_BIOTECH_DRAFT_TRAINING_COURSE_2020_FINAL_v10.pdf
 
Description SRA Payam Mehrshahi presented at the EIT food workshop ALGAL BIOTECHNOLOGY 2020 - TECHNIQUES AND OPPORTUNITIES FOR THE SUSTAINABLE BIOECONOMY 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact In 2020 due to the COVID restrictions, the EIT Food professional development course ALGAL BIOTECHNOLOGY - TECHNIQUES AND OPPORTUNITIES FOR THE SUSTAINABLE BIOECONOMY was held as a hybrid course. This course was developed and led by colleagues at The University of Cambridge (UK), Matis (Iceland) and Fraunhofer (Germany). The course attendees were graduate, postgraduate and industry professionals who are interested in gaining exposure to the latest insight into technical, commercial and policy concepts that impact algal biotechnology. Payam's talk titled "Genetic Engineering Approaches For Algal Biotechnology" was followed by a Q&A session. The range of questions was testament to the diversity of interests and stage in career of those in attendance.
Year(s) Of Engagement Activity 2020
URL https://www.eitfood.eu/projects/algal-biotechnology-techniques-and-opportunities-for-the-sustainable...
 
Description Talk at Diabetes Unit, KEM Hospital, Pune India 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk given to clinicians, scientists and Government officials in India to explain the biochemical basis of Vitamin B12 metabolism and how this micronutrient might be obtained from microalgae foodstuffs. As a result, a dietary intervention trial with over 500 volunteers has been set up by the hospital and the outcome will provide essential information to help formulate appropriate 'high vitamin' snacks. In return we have initiated a further interaction to study the effect of B12 deficiency on the human gut microbiome
Year(s) Of Engagement Activity 2019