The Nucleate Artery: New Ways to Listen to Your Heart, Stress Regulation in Bacteria, and Thoughts about Living a 100 Years!
The Nucleate Artery: New Ways to Listen to Your Heart, Stress Regulation in Bacteria, and Thoughts about Living a 100 Years!
PLUS: We speak with A/Prof. Jeremy Lim, Co-Founder and CEO at Asian Microbiome Library (AMILI) on Nucleate Singapore Pulse
Welcome to the third issue of The Nucleate Artery. Please send us your feedback, we want to know how we can make this reading experience more enjoyable for you.
WE START WITH EXCITING NEWS: Nucleate Singapore is co-organising our first startup social event 🥂 with LKCLearn! We have invited the founders of two local biotech startups, Volker Patzel, PhD, Co-founder and CEO of Avecris, and Natasha Hui Jin Ng, PhD, Scientific Co-Founder and Advisor of BetaLife to share their origin stories and journeys into the industry.
We also have REFRESHMENTS, generously sponsored by Proteintech. But most of all - we’re excited to connect with you in person, so save the date and let’s build a closer biotech community together!
IN THIS ISSUE: we discuss cardiovascular health tracking, a novel mechanism of stress regulation in bacteria, and healthy longevity.
It’s a long and exciting one, so grab a coffee ☕ and settle onto a seat!
Here we go!
🍽️ Digestibles
(Research that has been published within the past 2 months)
1. New ways to listen to your heart: revolutionising cardiovascular health tracking
Did you know that cardiovascular disease holds the top spot as the world's leading cause of mortality? It claims around 17.9 million lives annually, a staggering 85% attributed to heart attacks and strokes, many of which are preventable if caught early. Optical sensors have proven their worth in our everyday lives (think wearables like your Apple Watch or Garmins), but in disease monitoring, we need more than just basic measurements like blood oxygen levels and heart rate. In this exciting development, first authors Jin Haoran and Zheng Zesheng, in a team co-led by Prof. Zheng Yuanjin (School of Electrical and Electronic Engineering) and Prof. Chen Xiaodong (School of Materials Science and Engineering) from NTU, developed an optoacoustic blood "stethoscope” (OBS). This device functions as an adhesive wearable ultrasound device that can provide information on not only heart rate and blood oxygen, but also drug levels and the state of your blood vessels and cells. It can even construct a 3D image of your vessel!
An illustration of the optoacoustic blood "stethoscope” (OBS) laminated on the surface of the hand. Figure reproduced from Jin, H., Zheng, Z., Cui, Z., Jiang, Y., Chen, G., Li, W., ... & Zheng, Y. (2023). A flexible optoacoustic blood ‘stethoscope’ for noninvasive multiparametric cardiovascular monitoring. Nature Communications, 14(1), 4692.
🍪 Bite-sized Analysis
The promise of this technology is that it revolutionises the way we manage cardiovascular health. In a clinical setting, it will make it easier for doctors to measure treatment effectiveness, or researchers to monitor clinical trial patients remotely. But there’s more, given that we are often barely an arm’s length away from our phones, we could just be pinged if anything is amiss. Users or caretakers can be warned that that bout of dizziness or shortness of breath should not be dismissed, that getting it checked can make the difference between life and death. People at risk of cardiovascular diseases can take charge of their health, and those in hazardous or physically demanding environments, such as high altitude or high pressure, can be warned of safety limits. In the future, tweaking laser wavelengths may even allow it to measure pH values, blood glucose, blood temperature, and maybe even monitor tumour-treatment. Summarily, it is a device worth watching (pun not intended 😉).
2. ROS-directed translational regulation in Enterococcus faecalis
Reactive oxygen species (ROS) are a natural consequence of aerobic respiration. Excessive ROS levels incur molecular damage, disrupting essential physiological functions. For bacteria, ROS stresses can additionally be induced through antibiotics or introduced by immune cells like phagocytes. Naturally, organisms have developed defence systems that neutralise ROS to mitigate its detrimental effects. That said, bacteria’s ROS exposure response mechanism can take a troubling turn as the same mechanism in overcoming ROS can aid in the process of antimicrobial resistance (AMR), which continues to stand as one of the top 10 global public health threats according to WHO. Thus, understanding how bacterial adapts to ROS stress can be a first step to develop novel AMR therapies. The work by first author Dr. Lee Wei Lin, Ph.D. and the team led by Prof Peter C. Dedon from Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) at Singapore-MIT Alliance for Research and Technology (SMART), sheds light on a novel response mechanism to ROS sensing in a common gut bacterium, Enterococcus faecalis, through a specific RNA modification, 2-methyladenosine (m2A) that can be a target for drug development. This mechanism has a more immediate response in the m2A modification than gene expression control because it directly targets the 23S rRNA and tRNA – machineries that are responsible for protein production. Overall, this work unveils a new layer of bacterial stress adaptation and offers insights into potential avenues for combating AMR.
🍪 Bite-sized Analysis
Apart from bacteria, RNA modifications in response to stresses in humans have been extensively studied by this research group. We now know over 170 different chemical modifications on RNA. Despite knowing of these RNA modifications, their precise regulation and functions remain enigmatic. Collaborating with Prof Thomas J. Begley from RNA Institute, University at Albany, they pioneered the field of tRNA epitranscriptomics; a field which they have envisioned to have applicability in cancer therapeutics since 2013. The suggested approach mirrors the antimicrobial strategy in E. faecalis, enabling cancer cells to yield to ROS or stresses. Notably, the team's endeavours extend to the startup, HOVANA, which focuses on precise medicines for correcting disease caused by disarray in protein production. By understanding the underlying mechanisms of these modifications, how they occur, and their potential biological significance, coupled with the progress of tRNA therapeutics, there is the potential of unlocking new means of treatments. The horizon holds promise for tRNA therapeutics' emergence in clinical trials.
tRNA-modifying enzyme and linked neurological and metabolic disorders. Figure reproduced from [4]. Pereira, M., Francisco, S., Varanda, A. S., Santos, M., Santos, M. A., & Soares, A. R. (2018). Impact of tRNA modifications and tRNA-modifying enzymes on proteostasis and human disease. International journal of molecular sciences, 19(12), 3738.
🥡 Event Takeaways
At the end of August, we attended the SGInnovate event 'Longevity and Healthspan 101', featuring Dr. Ryan Ware, MD, MS, co-founder and Chief Medical Officer at Mito Health, Levana Sani, co-founder at NalaGenetics, Assoc Prof Dr. Jan Gruber, PhD, and Peter Ward, co-founder and CEO of Humanity.
Standing room left only! 👆
Our motivation for attending this event is simple: as Singapore is investing heavily – in new preventative care strategy Healthier SG – over $1 billion in set-up costs and $400 million in yearly recurrent expenditures 💸 [1], we wanted to know how biotech inserts itself in this shared endeavour of what could be qualified as “better” lives (at least, on the health aspect of things, physical and mental).
When we got to 32 Carpenter Street, the first thing that we noticed was the crowd. It was a very popular event, online registration was closed weeks before the event date (many of our friends could not sign up for it). And, even though on-site registration was made available for last minute attendees (we dragged our friends who were not able to not sign up online), there were just not enough seats for all of us.
Dr. Ryan Ware, MD, kick-started the event by qualifying for the audience how an average life fares against the Quality of Life (QOL) metric:
QOL is a measurement of how we perceive various aspects of our lives, including physical health, functional capacity, and emotional and social well-being [2].
The pain point: QOL ↓ as years lived ↑
Dr. Ware began by describing a natural phenomenon of a gradual decline in QOL as we live more years. Indeed, with every birthday celebration is the decline of our physical bodies; in slowed metabolism, clicking knees, and the loss of some youthful perkiness that we once had 🫣. When this happens, our QOL decreases.
While it is inevitable that QOL will decrease as we age, we can still attempt to prolong a quality of life, spent in "good health, free from the chronic diseases and disabilities of ageing”. This period is also known as our healthspan [3].
The solution: Leverage genomic data to optimise health and increase healthspan
One way to prolong good health is by optimising our lifestyle. For both Mito Health and NalaGenetics, this optimization is led by data, more specifically, our unique genetic makeup – our ATGCs!
The human genome is three billion base pairs long. Every unique individual carries codes within their genome that influences how their bodies interact with the external environment, which includes the foods we eat, sleep, exercise, and the medication we take. These interactions can then affect how the body ages over our lifespans and how we experience disease. Therefore, by interpreting genomic information, these startups can offer personalised health analyses and recommendations to find the best lifestyle plan (Mito Health), and optimised medication and nutrition plans (NalaGenetics).
The use of genetic data to inform expected bodily responsiveness is not new. Of note, in 2006, the U.S. Food and Drug Administration (FDA) approved a genetic lab test to support physicians in assessing patient susceptibility to warfarin, a blood thinner prescribed to prevent blood clots [4,5]. Carriers of the common variant gene have impaired warfarin metabolism (~90% decrease in catalytic efficiency in vitro!) [6,7], requiring a reduction in the maintenance dosage of warfarin to avoid over-anticoagulation and serious bleeding.
Similarly, genomic data can be interpreted to inform our lifestyle choices so that healthspan can be increased. However, as with all lifestyle recommendations, one possible issue would be the consistency and discipline needed to adhere to the personalised lifestyle plan. Motivation may wane after several weeks, and as beings of habit, we must exert extra willpower to change our lifestyle (and doing this is never easy). Both startups acknowledge this issue, and encourage adherence through continuous support, either in the form of consistent followup check ups or accessible online support!
Graph reproduced from Mito Health👆 The target is to spend more years in good health, and fewer experiencing poor quality of life (move from A → B).
Implications to a longer life: What do we do with the extra time?
Later, we were asked to answer a simple poll question: I want to live to be 100 years old: Yes/No? Around 75% of the attendees answered with a ‘Yes’. It was obvious to us that we were a part of a crowd who cared about how their lives could be led better and longer. During the Q&A, there were many questions being raised about specific supplements to take, sleep optimisation and stress management; people want the manual to lead a better and healthier life.
It is interesting to wonder how the extra time could be used. We know some want to witness the colonisation of Mars, while others want to spend quality time with their grandchildren in good health. Along a more creative vein, it would also be possible to max out the 99-year HDB housing lease if we live for a century 🤣😅, and to watch a tree reach maturity – some of these trees take 100 years!
Access to technology: Is a longer life only for the rich?
Towards the end of the event, the crowd pivoted towards deeper and harder ethical questions that revolve around these technologies (we love these!).
There were discussions about how the technology may have an unequal distribution in society, especially given the high price points (Mito Health costs SGD$599, and NalaGenetics ~SGD$200 - $500). In view of its potential to improve health, which can be approached as a basic human right [8], concerns were raised about making this technology accessible to everyone, a stand that is also reflected in other national efforts in the longevity space [9].
These sentiments were summed up nicely in a question an attendee asked:
“How can we make longevity a national healthcare imperative?”
How technology interacts with society is a complex matter; given how nascent the provision of this technology is, the panel emphasised on first tracing the impact of their product to collect data, which can then be used to facilitate conversations with various other stakeholders, including insurance product providers and policymakers. Admittedly, these are not questions that can be answered over a 30-min Q&A. Still, we enjoyed witnessing a passionate and thoughtful audience who understood the far-reaching implications biotech could have on society.
Given the global shift in age demographics, research in healthy longevity is bound to become increasingly relevant and important to societies. We are excited to see how this field will develop over the next decade and more!
🎧 Nucleate Singapore Pulse
📓 View episode show notes and transcript
Who did we interview?
Nucleate interviewed A/Prof. Jeremy Lim, MBBS, MPH, MRCS (UK), FAMS, and also Co-Founder and CEO at Asian Microbiome Library (AMILI) who is a surgeon by training and has transitioned from surgical practice to healthcare management, policy work, and entrepreneurship.
What did we talk about?
A/Prof. Lim delves into his venture, AMILI, and its mission to build the world's largest multi-ethnic Asia gut microbiome database. He also talks about the importance of shifting from a sick care model to a health care model and the role of healthcare financing in promoting health outcomes.
An interesting fact
AMILI is building a huge multi-ethnic repository of microbiome data and samples from Asia, including the only existing microbiome bank in Southeast Asia. It is also developing diagnostics tests, predictive algorithms, and microbiome-modifying interventions through its proprietary analytics engine called AMILI Prime.
📆 Events happening this month
Entrepreneurship
Explore how technology can enhance healthcare outcomes and reduce costs with speakers from AWS and DxD Hub in this panel discussion organised by co11ab.
[21 Sep 2023, 2:00 PM - 4:00 PM SGT, In-person]
Impacts of Technology and Startups on Singapore’s Health Innovations
This webinar by JPP - Life Sciences Marketing offers a solution to the challenge of effectively communicating your expertise in your field.
[25 Sep 2023, 10:00 PM - 11:00 PM SGT, Online]
Policy and Regulation
This FDA regulatory training course by Educo Life Sciences covers processes, terminology, and best practices for positive interactions with the FDA.
[28 Sep 2023, 4:30 PM - 11:00 PM SGT, Online]
Understanding US FDA Regulatory Affairs | 1-Day Live Online Training
Discovery
The Boston Epigenetics Society talks to K36 Therapeutics, a biotech startup focused on the clinical development of KTX-1001, an orally bioavailable inhibitor of an epigenetic regulator implicated in developmental disorders.
[22 Sep 2023, 12:00 AM - 1:15 AM SGT, Online]
Dr. Louise Lafortune's talk organised by MOH and Duke-NUS will discuss the global challenge of ageing populations in Asian economies.
[26 Sep 2023, 4:00 PM - 5:00 PM SGT, Online]
SCSS/CTFG-IMCB organises a panel discussion on the emerging trends in biotech.
[3 Oct 2023, 11:00 AM - 12:30 AM SGT, In-person]
Network
Network with early-stage different players in Singapore’s biotech startup ecosystem over a casual coffee in this event organised by AWS.
[11 Oct 2023, 9:00 AM - 11:00 AM SGT, Online]
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