How does diet improve metabolic health? Dissecting bioenergetic pathways altered by diet using genomic approaches (TRAKA_F17DTP1)
Lead Research Organisation:
University of East Anglia
Department Name: Graduate Office
Abstract
Broccoli-rich diets have been associated with reduced risk of developing a range of chronic diseases, such as cardiovascular disease and certain cancers. We have recently showed that consumption of broccoli rich diets reduces LDL cholesterol and fasted glucose levels, which suggests that broccoli modulates central metabolic pathways in a manner that may protect against development of chronic diseases. Broccoli is rich in glucoraphanin, a sulphur-containing glucoside that though not bioactive itself is readily metabolised in the gut to bioactive sulforaphane. By using cell and animal models sulforaphane has been linked to the activation of a key transcription factor, nuclear factor-erythroid 2 like 2 (NRF2), which is responsible for upregulating a host of antioxidant genes by binding to a defined element within their promoter. Recent evidence suggests that NRF2 may also play a role in modulating energy metabolism that though under-explored is likely the mechanism by which broccoli-rich diets promote good health. This PhD project will focus on studying the importance of NRF2 activation in mediating the changes in liver metabolic pathways that can maintain health. This project will, first, use whole genome sequencing techniques to identify the transcriptional cascades that are altered by broccoli bioactives and NRF2 and understand their effect on fatty acid metabolism and cellular bioenergetics. There will also be opportunity to engineer novel genetic knockout human cells through genome editing to specifically understand the importance of nrf2 in mediating metabolic regulation by dietary bioactives.
People |
ORCID iD |
| Maria Traka (Primary Supervisor) | |
| Federico Bernuzzi (Student) |
| Description | Although this is still very early days, using genome editing I have been successfully to remove the function of a Transcription Factor. By removing the function of this transcription factor I have already seen a reduction in activity of a protein that has been established to be a well known metabolic regulator. |
| Exploitation Route | Gaining but understanding on the molecular mechanism by which these proteins affect metabolism may target pharmaceutical companies to develop new drugs that can increase or inhibit the acitivity of these proteins for promoting health or preventing formation of chronic diseases |
| Sectors | Education,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | Doing outreach acitivites to school and the general public, by sharing the health benefits of eating Cruciferous Vegetables |
| First Year Of Impact | 2018 |
| Sector | Agriculture, Food and Drink,Education,Healthcare |
| Impact Types | Societal |
| Title | CRISPR/Cas9 |
| Description | Utilsing genome editing CRISPR/Cas9 to Knockout a protein in liver cells |
| Type Of Material | Cell line |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | The transfection has been successful and currently assessing downstream consequences. It is still very early days |
| Description | Collaboration with MyDNAhealth |
| Organisation | My DNA health |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Assessed the literature to determine whether the sufficient evidence to develop a kit to personalize exercise to individuals. Outcome there is not |
| Collaborator Contribution | MyDNAhealth is currently collaborating with the Food Data Banks department from the Quadram Institute, and trying to develop online platforms that can also be used on the phone such as an App in order to personalize Nutrition |
| Impact | Personalized Nutrition platforms |
| Start Year | 2018 |
| Description | Collboration with Prof Karsten Hiller from Technical University of Braunschweig |
| Organisation | Braunschweig University of Technology |
| Department | Helmholtz-Zentrum für Infektionsforschung |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Spent 6 weeks in Germany to utilise methods and instruments that are not available at the Quadram Institute, using labelled isotopes of certain molecules such as glucose and glutamine to understand how the cells metabolize them. |
| Collaborator Contribution | Data Analysis |
| Impact | Brought back from Germany skills on how to conduct this type of assement |
| Start Year | 2019 |
| Title | ESCAPE and ADAPT study |
| Description | Our research group for the past couple of years have started undertaking human intervention studies looking at the effects of dietary bioactives found in Broccoli to men with prostate cancer under surveillance. This Broccoli has been enhanced by breeding it over many generations and it contains a much higher glucosinolate content , these are the Sulfur compounds present in Broccoli. I am currently helping a urologist who is currently undertaking a Medical Doctorate on a study looking at a bioactive in Broccoli and garlic to see its effect on prostate cancer progression |
| Type | Preventative Intervention - Nutrition and Chemoprevention |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2017 |
| Development Status | Under active development/distribution |
| Impact | One of the study has been published. |
| URL | https://www.ncbi.nlm.nih.gov/pubmed/30982861 |
| Description | Norwich Science Festival |
| 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 | QIB activity tables and art exhibition |
| Year(s) Of Engagement Activity | 2019 |
| Description | On the 2nd of July the Quadram Institute of Biosciences (Norwich UK) hosted the event organised from the IFST, by streaming the lecture given by Professor Michael Gibney, Emeritus Professor of Food and Health from University College Dublin |
| 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 | Media (as a channel to the public) |
| Results and Impact | The event was organised from Federico Bernuzzi and Dr Anabel Mulet Cabero from the Quadram Institute of Biosciences (QIB), in partnership with the IFST Eastern Branch. 25 people attended the lecture, mainly staff from the QIB but also several additional employers across the Norwich Research Park and additional companies across Norfolk. Prior to the lecturer Dr Jennifer Ahn-Jarvis a Research Scientist from the QIB, gave a 30-minute lecture on her Post-Doctoral Followership work at Ohio State University. The event ended with a 1hour networking session, were cold food and drinks was provided. This year's event had the largest number of attendees, compared to previous years and the feedback that was provided was that it was very well organised, and both talks were well received Federico Bernuzzi got in touch with Dr Patricia Hart to ask whether the Quadram could host the event. He then organised the speaker. Dr Mulet Cabero instead sorted out the advertisement, by publishing information on the Quadram news and was in charge of the catering |
| Year(s) Of Engagement Activity | 2019 |
| Description | Public Engagement at the Royal Norfolk Showground on the 26th of June |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Teaching the public the health benefits of dark chocolate, blueberries and broccoli. For the kids an activity was given them to do. Three different pots that had dark chocolate, broccoli and blueberries and the kids had to smell and guess the compounds |
| Year(s) Of Engagement Activity | 2019 |
| Description | School Visit (Hethersett Primary School) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Attended a morning at a local primary school in Hethersett Norwich. 60 pupils were split into five different groups. Five different stations were set up and each station represented different food nutrients such as carbohydrates, protein,fats. The aim of the activity was to teach the children which foods had those particular nutrients whether health choices could be chosen to ultimately improve their health style. |
| Year(s) Of Engagement Activity | 2020 |
| Description | School Visit (Hethersett Secondary School) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Smell test activity. Students were split into differen groups and pots containin different smelly food componentns such as Broccoli, garlic, chocolate, had to smell the pots and guess what food item it was and in particular why do different foods smell differently. |
| Year(s) Of Engagement Activity | 2018 |