Dr Weng Ng joins Research Complex at Harwell as a group leader this autumn following his appointment as a Wellcome Early Career Fellow. Working across eBIC, Diamond Light Source and Research Complex, his project is titled “Structure and native functionality of the glycoproteins presented by zoonotic bornaviruses”.
Previously, Weng was based at The Jenner Institute, University of Oxford, as a postdoctoral researcher in Structural Vaccinology, studying the rabies virus with Dr Sandy Douglas. Weng began his studies in Biochemistry at Imperial College London, completing his BSc before moving to Oxford for a DPhil in Cellular Structural Biology.
Read our interview with Dr Ng to discover more about the process of applying for fellowships, how AI might enhance our understanding of viruses, and why Research Complex provides the ideal base for cutting-edge structural biology.
Where did your original motivation to study science come from?
From an early age, my fascination with the wonders of science began with astronomy and later expanded into the world of palaeontology. Planets, stars, and dinosaurs acted as my gateways into the realm of science, shaping my curiosity as they often do for many young minds. Thankfully, my parents actively encouraged and nurtured this inquisitive spirit (I was never found without books about galaxies and dinosaurs!), fostering my passion for exploration and innovation, which has persisted throughout my academic pursuits.
As my interests evolved in school, I grew to appreciate the deep connection between scientific discoveries and their real-world applications. The convergence of basic and applied science during my career led me to delve deeply into the study of virology and associated pathology, where I now focus my efforts to harness scientific knowledge to inform and rationalise therapeutic strategies.
How did you identify your interest in structural biology, and subsequently your research specialism in glycoprotein structure and the pathobiology of viruses?
Interestingly, I had initially wanted to be a geneticist, motivated by a genetic condition prevalent in my family. However, my trajectory shifted entirely after a hands-on research experience ten summers ago at the Membrane Protein Laboratory, Research Complex, and Diamond X-ray synchrotron, where I developed my profound interest in structural biology.
The ability of this technique to construct intricate molecular blueprints for analysis and manipulation mesmerised me. Indeed, the role of structural biology in deciphering mechanisms and guiding stabilising mutagenesis became indispensable in my study of virus-host interactions, providing crucial insights into infection biology and therapeutic design. I chose to focus on virus glycoproteins due to their prominent display on the virion surface – a feature that renders them the primary determinant of cell, tissue, and host tropism, thereby serving as main targets for host humoral immune responses.
Why viruses? Because they are incredibly ‘smart’. And my goal is to outsmart them.
Congratulations on your Wellcome Early-Career Award. How did you find the process of creating your research proposal?
Thank you! The process was a lengthy one! The entire journey, from conceptualising the project to receiving the award, spanned about two years. Upon finalising the project idea, I proactively engaged with numerous national and international researchers to establish collaborations and gather preliminary data. These initial steps were crucial in outlining the project’s scope, ambition, and feasibility. Simultaneously managing the research groundwork, navigating the vigorous application process, and handling various administrative tasks, all while fulfilling my (previous) role as a postdoctoral researcher at the University of Oxford, made this period undoubtedly one of the most challenging in my career.
Have you benefited from the mentorship of any senior scientists in your career to date? How did their influence shape your own research approach?
I have been fortunate to shape my career through the invaluable mentorship of esteemed senior colleagues. During my DPhil studies at Oxford, I had the privilege of learning essential skill sets from my supervisor, Professor Thomas Bowden. Under his guidance, I learned to formulate ambitious yet tractable research inquiries and to refine my manuscript writing abilities. Moreover, my colleague Max Renner, formerly a postdoctoral fellow at Oxford and now an Assistant Professor at Umeå University, imparted profound insights into navigating the innate difficulties of scientific research (e.g., frequent experimental setbacks, uncertainties of job security in academia) while maintaining a resilient and passionate spirit.
What has been the most challenging phase or task of your career so far?
As I mentioned, navigating the scarcity and intense competition for research funding, coupled with the precarious nature of job security in academia, had been undeniably stressful. At one point, I found myself contemplating a departure from academic research, exploring options in the industrial sector, or even leaving scientific research altogether. The landscape of fixed-term postdoctoral contracts, often lasting 1-3 years, demands substantial time spent seeking the next opportunity/contract, all while striving to amass experience and publications essential for grant/fellowship applications, and simultaneously balancing personal life, family, and finances. The uncertainty and instability during this phase of my career significantly contributed to distress and anxiety.
Eventually, I decided to take a ‘gamble’ by focusing on a few independent fellowship applications instead of transitioning from one postdoc position to another (I even declined a postdoc offer elsewhere). While I am grateful that this strategy worked out for me, I cannot claim that it was an ideal solution, if such a solution even exists. Even now, the prospect of constant grant applications and renewals to extend my academic career or secure a permanent position continues to weigh on my mind.
This challenge is not unique to me but is rather a shared experience among researchers navigating academia. Addressing this issue requires collective efforts involving researchers, universities, institutes, research councils, and funding bodies. I sincerely hope that ongoing discussions about these challenges will lead to meaningful changes that promote equality and stability within academic careers.
We are so pleased you have chosen to base your group at Research Complex. Can you tell us what it is about the facilities here that supports your research?
The Research Complex's integration with various academic institutes and cutting-edge research facilities, such as the Diamond Light Source, forms a dynamic hub and promotes seamless research workflow, particularly benefitting structural biologists. The capacity to perform sample preparation, biochemical, and biophysical characterisations crucial for projects in structural biology and virology aligns perfectly with my research needs. Additionally, Harwell Campus serves as a major meeting point for esteemed national and international scientists, fostering a culture of idea exchange and collaboration. This environment consistently generates stimulating data, welcomes diverse expertise, and stimulates innovative thinking, making the Research Complex an enriching space for both research endeavours and the researchers themselves.
What do you hope will be the impact of your research field in the medium and long-term future?
The evolution of structural biology has been extraordinary, encompassing the elucidation of molecular machineries in cellular processes and catalysing the development of biomedical therapeutics. Rapid advancements in high-resolution electron cryo-microscopy techniques and artificial intelligence have ushered the field into a new era, resulting in a proliferation of both experimental structures and predicted models.
As structure prediction becomes increasingly prevalent in the near-to-medium future, the critical necessity for rigorous structural and functional validation of bioinformatically guided designs and models becomes imperative to bridge the gap between AI-driven hypotheses and actual experimental outcomes. Hence, one of my research endeavours aims to establish a streamlined structural virology pipeline that expedite experimental validations, particularly focusing on viral surface glycoproteins, thereby augmenting vaccine design initiatives.
Another facet of my research involves harnessing the abundance of data, models, and databases to guide in silico optimisation of monoclonal antibody-based therapies – an indispensable avenue complementing vaccine development. This, I believe, entails the long-term impact of AI-assisted structural biology, enabling researchers to navigate swiftly through high factorial possibilities, accelerating therapeutic development from research to market.
An essential emphasis lies in the significant growth of artificial intelligence, which potentially reshapes our conventional perception of short, medium, and long-term timelines. In the realms of computers and AI, what might seem like a year could equate to a considerable duration!
Beyond your own field, how optimistic do you feel about the state of scientific research? What challenges do you believe face the Science community?
I hold a positive outlook on the current state of scientific research and the scientific community. There is a noticeable shift in grants and fellowships, adopting a more flexible approach to eligibility criteria, such as considering an extended eligibility duration after obtaining a PhD, and prolonging grant durations to facilitate more substantial and impactful research. Re-entry awards also provide valuable support to individuals seeking to re-join research following a career break. Moreover, I am pleased to see an increasing number of researchers and journals embracing the principles of open access, which promotes greater accessibility and transparency of scientific findings.
However, there appears to be a lack of incentive to communicate our research endeavours to the non-scientific public. This gap often leads to misunderstandings and misconceptions of how science operates. For instance, the rampant misinformation and disinformation surrounding vaccines during the COVID-19 pandemic was deeply disheartening. I strongly believe that without a robust bridge between scientists and the general public, the credibility and trust in our work can be easily undermined. Therefore, it is imperative to actively convey our scientific pursuits in an accessible and engaging manner, especially when tackling highly technical subjects.
Another major challenge is access to funding and resources, particularly for low- and middle-income countries struggling to establish research and biomanufacturing facilities. In contrast, high-income countries often possess advanced facilities and greater resources. This stark imbalance became evident once more during the COVID-19 pandemic, notably in global vaccine production and distribution, underscoring the glaring disparities in scientific knowledge and resources worldwide. Addressing viral outbreaks demands a concerted global effort rather than isolated national endeavours. For instance, achieving measles elimination requires protection in all countries, showcasing the interconnectedness of global health challenges. To prevent the recurrence of such inequities, it is crucial for high-income countries to support lower-income nations in procuring, producing, and distributing vaccines. This effort requires collaborative initiatives aimed at bolstering the capabilities of under-resourced countries, ensuring equitable access to critical resources and scientific advancements on a global scale.