The clichés we use become so downtrodden that we often say them without thinking. How many times, for example, have you said you went with your gut on a certain decision?
As with many of these aphorisms, there appears to be genuine wisdom behind it. Scientists are learning all the time about the links between our guts and our brains, and recent findings from a California Institute of Technology-led (Caltech) study have added to our understanding of what’s going on behind our belly buttons.
This research contends that a particular molecule, produced by our gut bacteria, has contributed to anxious behaviour in mice. The Caltech researchers say that a small-molecule metabolite that lives in the mouse’s gut can travel up to the brain and alter the function of its cells. This adds further grist to the belief that there is a link between our microbiome, brain function, and mood.
The researchers behind the Nature paper say previous studies found that people with certain neurological conditions have different gut bacteria communities. Furthermore, studies in mice revealed that manipulating these communities can alter neurological states.
Their study investigated the bacterial metabolite 4-ethylphenyl sulphate (4EPS) that is produced in the intestines of humans and mice and circulates throughout the body. In particular, they focused on the effect of 4EPS on mouse anxiety. For the sake of the study, mouse anxiety measured the creature’s behaviour in a new space - whether it hid in a new space as if from a predator or whether it was willing to sniff around and explore it.
The researchers compared two groups of lab mice: those colonised with pairs of bacteria that were genetically engineered to produce 4EPS, and a second group that was colonised with similar bacteria that couldn’t produce 4EPS. They then observed the rodents’ behaviour after being introduced to a new area.
Some mice become anxious when introduced to new spaces, and this is reflected both in the gut and the brain.
The results were very interesting indeed. The researchers observed that the group of mice with 4EPS spent far less time exploring this new place and more time hiding compared to the second group of non-4EPS mice. They also found that brain regions associated with fear and anxiety were more activated within this first group.
>> Interested in drug discovery? Why not attend our upcoming event at the Francis Crick Institute, London, UK.
When the mice were treated with a drug that could overpower the negative effects of 4EPS, their behaviour became less anxious. A similar study in Nature Medicine also found that mice were less anxious when treated with an oral drug that soaked up and removed 4EPS from their bodies.
The Caltech-led research could inform our understanding of anxiety and mood conditions.
‘It’s an exciting proof-of-concept finding that a specific microbial metabolite alters the activity of brain cells and complex behaviours in mice, but how this is happening remains unknown,’ says researcher Sarkis Mazmanian, in whose laboratory much of the research took place.
‘The basic framework for brain function includes integration of sensory and molecular cues from the periphery and even the environment. What we show here is similar in principle but with the discovery that the neuroactive molecule is of microbial origin. I believe this work has implications for human anxiety or other mood conditions.’
So, our predecessors were right: there’s a lot more to those gut feelings than you think.
>> Read the Nature paper on the Nature magazine website.
Continuing our series on Black scientists, Dr George Okafo tells us about his journey from curious child, encouraged by family and mentors, to Global Director of Healthcare Data and Analytics with a leading pharmaceutical company.
What is your current position?
I am Global Director, Healthcare Data and Analytics Unit at Boehringer Ingelheim, and have been in this role for the past 10 months.
Right: Dr George Okafo
Please give us a brief outline of your role.
To build an expert team of data stewards, data scientists and statistical geneticists tasked with accessing and ingesting population-scale healthcare biobanks and then deriving target, biomarker and disease insights from this data to transform clinical development and personalise the development of new medicines.
What was it that led you to study chemistry/science and ultimately develop a career in this field? Was this your first choice?
My interest in science stems from my parents. My father was a medical doctor, and my mother was a senior midwife. As a child, I was always very curious and wanted to know why and how things worked. This curiosity has stayed with me all my life and throughout my career at GlaxoSmithKline and now at Boehringer Ingelheim. In my current role, I am still asking the same types of questions from Big Data and these answers could have a profound impact in the development of new medicines.
Was there any one person or group of people who you felt had a specific impact on your decision to pursue the career you are in?
Yes, my father and mother, who supported, encouraged and gave me the confidence to be curious, to keep trying and to never give up.
Dr Okafo held senior director-level roles in drug discovery and development while at at GSK.
Could you outline the route that you took to get to where you are now, and how you were supported?
My career journey started at Dulwich College (London) where I studied Chemistry, Biology, Maths and Physics at A Level. This took me to Imperial College of Science, Technology and Medicine (London), where I completed my Joint BSc in Chemistry and Biochemistry and my PhD in Cancer Chemistry.
I then spent a year at the University of Toronto in Canada as a Postdoctoral Fellow, before embarking on my career in the Pharmaceutical Industry, starting at GlaxoSmithKline (GSK). I spent 30 years at GSK, where I held many senior director-level roles in drug discovery and development. During my time, I made it my mission to learn as much about the R&D process and used this knowledge to understand how innovation can impact and transform drug research.
I have been very fortunate in my career to be surrounded by many brilliant and inspirational people who had the patience to share their knowledge with me and answer my many questions.
>> Curious to read more about some of the great Black scientists from the past? Here’s our blog on Lewis Howard Latimer.
Considering your own career route, what message do you have for Black people who would like to follow in your footsteps?
Surround yourself with brilliant people who can inspire you. Look for people who you respect and can coach and mentor you. Don’t be afraid to fail. Work hard and keep trying.
What do you think are the specific barriers that might be preventing young Black people from pursuing chemistry/science?
No, I do not see colour as a barrier nor a hindrance to pursuing a career in science. I think it is important to look for role models from the same background to help inspire you, to answer your questions and to encourage you.
What steps do you think can be taken by academia and businesses to increase the number of Black people studying and pursuing chemistry/science as a career?
Have more role models from different backgrounds. This sends a very powerful message to young people studying science reinforcing the message… I can do that!
Could you share one experience which has helped to define your career path?
Not so much an experience, but a mindset – staying curious, inquisitive, always willing to learn something new, having courage that failure is not the end, but an opportunity to learn.
Antimicrobial resistance (AMR), now referred to as the silent pandemic, is causing governments, regulatory and health bodies to make a lot of noise.
Issuing a statement in late August 2021, the Global Leaders Group on Antimicrobial Resistance called on countries to ‘significantly reduce the levels of antimicrobial drugs used in global food systems’. The Global Leaders Group on Antimicrobial Resistance includes heads of state, government ministers and leaders from the private sector and civil society. It was established during 2020 to accelerate global political momentum, leadership and action AMR.
Co-chaired by Mia Amor Mottley, Prime Minister of Barbados and Sheikh Hasina, Prime Minister of Bangladesh, the Group is calling for all countries to take action to tackle the issue. Steps include: Ending the use of antimicrobial drugs that are of critical importance to human medicine to promote growth in animals, eliminating or significantly reducing over-the-counter-sales of antimicrobial drugs that are important for medical of veterinary purposes, and reducing the overall need for antimicrobial drugs by improving infection prevention and control, hygiene, bio security and vaccination programmes in agriculture and aquaculture.
Leaders are calling for the reduction in the use of antimicrobial drugs.
Speaking at the second meeting of the Global Leaders Group on Antimicrobial Resistance, Inger Andersen, Under-Secretary-General of the United Nations and Executive Director the United Nations Environment Programme said: ‘Already 700 000 people die each year of resistant infections. There are also serious financial consequences: in the EU alone, AMR costs an estimated €1.5 billion per year in health care and productivity costs…’ But Andersen added that now was an opportune moment to make change. ‘With concern over zoonotic diseases at an all-time high, governments can take advantage of the synergies available from tackling emerging disease threats concurrently. The Global Leaders Group has strategic access to forums to promote AMR integration in post-covid-19 plans and financing…It’s time to for us to act on the science and respond rapidly to AMR,’ Andersen said.
The Communiqué from the G7 Health Ministers’ Meeting held in Oxford, UK during June also gave significant space the AMR issue and the link with the pandemic. ‘We reiterate the need for ongoing education and reinforced stewardship of the use of antimicrobials, including avoiding their use where there is no science-based evidence of effectiveness. The pandemic has also highlighted the importance of infection prevention and control measures to tackle AMR, targeting both health-care associated and community-associated infections.’ Adding a sense of urgency the Communiqué continued: ‘We must act strongly and across disciplines if we are to curb the silent pandemic of antimicrobial resistance.’
A letter from the BactiVac Bacterial Vaccinology Network reminded the G7 Health Ministers that the 2016 O’Neill Report estimated that by 2050, 10 million lives each year and a cumulative US$100 trillion of economic output will be at risk due to increasing AMR unless proactive solution are developed now. In its letter to the G7, the Network issued this warning. ‘The headlines on AMR may have less immediate impact, but the news is no less stark. Over the long-term, AMR bacteria will cause more prolonged suffering than covid-19, with a more insidious impact on all our lives.’ Signatories to the letter included Professor Calman MacLennan, Senior Clinical Fellow and Group Leader, Jenner Institute, University of Oxford, Professor of Vaccine Immunology, University of Birmingham.
Researchers are collaborating to understand how AMR is impacted by a range of factors
The G7 also stressed the need for collaborative efforts for a better understanding of how AMR is impacted by a range of factors. Taking up this challenge; several initiatives has been put in place to study this. Most recently the United Nations Environment Programme and the Indian Council of Medical Research have launched a project looking at ‘Priorities for the Environmental Dimension of Antimicrobial Resistance in India.’ The project aims to strengthen the environmental aspects of national and state-level AMR strategies and action plans. In a similar development the European Food Safety Agency published an assessment of the role played by food production and its environment in the emergence and spread of antimicrobial resistance. Publishing the findings in the EFSA journal, the report indicated that fertilisers of faecal origin, irrigation and water are the most significant sources of AMR in plant-based food production and aquaculture.
Meanwhile, the first quarter of 2021 saw Ineos donate £100 million to the University of Oxford to establish a new antimicrobials research facility. The Ineos Oxford Institute for Antimicrobial Resistance aims to create collaborative and cross disciplinary links involving the university’s department of chemistry and department of zoology. The Institute also intends to partner with other global leaders in the field of AMR.
Partnering with India, the UK has committed £4 million to the AMR fight. With a total investment of £8 million, the partners have established five joint research projects which aim to develop a better understanding of how waste from antimicrobial manufacturing could be inadvertently fuelling AMR.
SCI has selected Harriet McNicholl from AstraZeneca as the 2021 National Undergraduate Placement Student of the Year.
The national undergraduate placement symposium brings together chemistry students undertaking industrial research placements each year. Students working in organic, biological, supramolecular, physical organic, medicinal chemistry and related fields are invited to submit posters. The finalists are then selected to present orally at the virtual symposium. This year’s applicants included students from organisations such as AstraZeneca, GlaxoSmithKline, UCB, Syngenta, Charles River and more.
Harriet McNicholl’s chemistry will be used to manufacture drug products to support patients in phase-II clinical trials.
As part of this symposium, Harriet McNicholl from AstraZeneca was invited to present her research to develop a safe, inexpensive and commercially viable process towards AZD5991, a candidate therapeutic for the treatment of acute myeloid leukaemia.
Encapsulating AstraZeneca’s dynamic and data driven approach to turning molecules into medicines, Harriet highlighted how the SELECT criteria, automation and High Throughput Experimentation were used to design and optimise a process. Harriet’s work aimed to maximise efficiency and sustainability, and her chemistry will be used to manufacture drug products to support patients in phase-II clinical trials.
Harriet is in the third year of her chemistry integrated Master’s degree (MChem) at the University of Liverpool and is currently undertaking a synthetic chemistry industrial placement within Chemical Development (CD) at Macclesfield.
‘I have thoroughly enjoyed my placement year within Chemical Development at AstraZeneca,’ she said. ‘It has been incredibly rewarding knowing the science I’ve worked on has the potential to fundamentally transform oncology patients’ lives. This opportunity has enabled me to develop many of my technical and soft skills and motivated me to pursue a career within the pharmaceutical industry.’
Dave Ennis, Vice President of Chemical Development for AstraZeneca in Macclesfield, said: ‘Congratulations to Harriet who has made significant contributions to our development activities in Chemical Development. It is a reflection of the quality of students we attract to our sandwich student programme; I’m proud that we give our students a great insight to drug development by being active participants in our projects, and it is highly motivating for our scientists in helping to coach and develop others - a win-win for all involved.
‘Over the past 25 years, we have had a successful rolling programme of sandwich students from a variety of universities that has helped to attract the next generation of scientific talent to AstraZeneca and the wider industry. Looking forward to our next cohort in 2021, and I’m sure they will compete for the prize next year’.
Harriet’s poster submission
Dr Andrew Carnell, Director of Year in Industry Courses at the Department of Chemistry in the University of Liverpool, added: ‘I am delighted that Harriet has been awarded this prestigious prize for her work during her placement at AstraZeneca. She is a credit to the department and to the university. Our Year in Industry students gain a huge amount from their placements, not only in terms of practical experience and technical knowledge but increased confidence and employability. Students return to us highly motivated for their final year and often go on to secure excellent and rewarding positions in today’s competitive job market.’
As part of this event, keynote speaker James Douglas (Manager of AstraZeneca’s Catalysis, High Throughput and Synthesis Technologies team) noted that his career journey started with a placement year at GlaxoSmithKline in Stevenage. James went on to describe the benefits of doing a placement year and how the skills he gained from his year in industry helped him to secure a Ph.D. at the University of St Andrews and a postdoctoral position with Eli Lilly in the United States.
This year’s competition featured many strong entries. Congratulations to runners up Daniella Hares (AstraZeneca, University of Southampton) for her presentation outlining computational techniques for drug discovery and poster prize winner Jake Odger (Sosei Heptares, University of York). The competition was hosted and organised by the Society of Chemical Industry Young Chemists’ Panel
For more on this year’s National Undergraduate Placement Student of the Year competition, visit: https://istry.co.uk/postercompetition/4/