The Nucleate Artery: Gut microbiome interaction replicated on a chip, and wait…when should you employ AI in your research?

Nucleate Singapore

Leong Kim Whye

Liyana Ayub Ow Yong

, and 2 others

Mar 15, 2024

We are The Nucleate Artery, a monthly newsletter focused on the latest biotech research and events in Singapore. Chat with us via our Slack community: @Liyana Ayub Ow Yong @Leong Kim Whye @Yeow Jiang @Ignacius Tay.

If you enjoyed reading this post, leave a comment and give us a like!

This month we will be hosting a Meet the (local) Start-ups social event, in partnership with NUS Mechanobiology Institute on 26 Mar, 5.30 pm. Join us as we discuss how Dr Shawn Hoon from Automera, and Dr Edward Chow from KYAN Therapeutics think AI and ML can complement drug discovery.

We look forward to seeing you at the event! Register here.

Happy March and happy reading!

🍽️ Digestibles

(Research that has been published within the past 2 months)

PRECISION IMMUNOTHERAPY: AI-assisted immune oncology platform to predict patient response!

The success of immunotherapy in blood-related cancers has sparked optimism for its potential in treating solid tumours. However, identifying patients who are likely to respond to these treatments remains a significant challenge. In a recent study by Tostado et al., the authors introduced an assay capturing head and neck cancer cell responses to natural killer (NK) cells by employing artificial intelligence to monitor and analyse these interactions. Through corresponding genetic studies of the grouped patient cell lines, they revealed a specific way these cancer cells were able to withstand NK cell attacks. This discovery unveils promising avenues for swiftly developing new strategies to tackle and treat cancer by deciphering how it evades the body's natural defences.

Labiotech covers extensively on the precision immunotherapy space!:

Learn more about CAR-NK therapy here!
Ten companies in NK cell therapy to watch out for 🤩
Check out the Beyond Biotech podcast as they interviewed Portage’s CEO, Dr. Ian Walters, and Artiva Biotherapeutics’ CEO, Dr. Fred Aslan

MICROBIOME: A miniature gut to peek into the tiny wonders at work!

By now, you've likely heard of "poop transplants" or Faecal Microbiota Transplants (FMT) used to treat colonic infections. While it is now explored for other conditions like Inflammatory Bowel Disease (IBD) and colorectal cancer, our understanding of how the trillions of microorganisms in our gut impact our health is limited by the lack of a suitable lab model to study this interaction. To address this, Lee et al. designed a scalable and realistic Gut Microbiome-on-a-Chip (GMoC) system that replicates the gut's structure and functions. In their study, harmful bacteria added to GMoC disrupted the cells and activated signals promoting tumour growth. However, these effects were counteracted by beneficial bacteria through competitive growth. The GMoC offers a realistic environment for studying gut microbes, unveiling insights crucial for disease understanding and microbe-based therapies.

Reproduced from Lee, J., Menon, N., & Lim, C. T. (2024). Dissecting Gut‐Microbial Community Interactions using a Gut Microbiome‐on‐a‐Chip. Advanced Science, 2302113.

Spring time for the Microbiota flora 🌷:

Dive deep with our local microbiome expert, Dr. Jeremy Lim, CEO and co-founder of Asian Microbiome Library (AMiLi), in this podcast by Nucleate SG Pulse team 🥳

Find out how the gut microbiome is associated with brain functions
OR how MaaT Pharma plan to use microbiome therapy to complement standard immunosuppressive drugs for acute graft-versus-host disease (aGvHD)

ANTIMICROBIALS: Conjugated oligoelectrolytes (COE) - molecular marvels at frontiers of antibiotic warfare

Mycobacteria (Mab) infections remain the most persistent with abysmal cure rates as a result of its resistance to first-line antibiotics. It often manifests as nontuberculous mycobacteria lung disease (NTM-LD) in patients with chronic lung diseases. A breakthrough strategy developed by Zhang et al., explores a new class of antibiotics that effectively targets essential pathways and disrupts mycobacterial membrane integrity. It comprises a flexible molecular framework (think swappable parts in a car!), that can be fine-tuned in a modular fashion. This strategy boasts a low cytotoxicity in mouse models of Mab lung infection, is less likely to lead to resistance, yet achieves desirable levels of effectiveness. As COEs represent a promising new class of antibiotics, this unveils the therapeutic potential of modular membrane-targeting drugs as potent anti-Mab candidates.

Oligoelectrolytes was initially developed to charge cellphones on the battlefield!:

Likewise, COEs were designed to be inserted into bacterial membranes to power electronic devices but got repurposed as potential antibiotics
Learn how else researchers plan to fight antibiotic resistance

Other biotech research we found:

In a concurrent study, the use of miniature tumours parallel to patients’ to guide personalised treatment in metastatic colorectal cancer
A screening workflow to help you design a higher quality CRISPR library!
A newly synthesised, longer lasting luteolin analog, LUA, for myocardial ischemia/reperfusion (I/R) injury

🥡 Event Takeaways

(Exclusive insights from biotech events in SG)

One rainy Friday in March, Liyana and Kimwhye attended the launch of the Singapore Clinical Research Professionals (SCRP) hosted by SGInnovate.

The SCRP association is a non-profit that aims to represent clinical researchers. Its initiatives include providing a channel for information sharing across expertise, idea development, and supporting meaningful connections in the clinical research space.

The forum attracted a very curated crowd. Many who came had years of experience running clinical trials or research labs, and others were weighty stakeholders in the clinical research space. It was a gathering that clearly mattered to the people; they were involved in a way that was uncommon in the local context. Singaporean scientists tend to make a shy community, usually making up an unassuming audience - but the crowd at this launch was spirited and inquisitive. Together with panellists A/Prof Danny Soon, Prof Dean Ho, Nate Zhang, Dr Jing Ping Yeo, and Dr Ivan Horak, the timeline and cost of clinical trials, and new to the landscape, digital therapeutics, were commented on and debated over.

Timeline of a clinical trial is long and complicated – any resources to get familiar?

Clinical trials involve risks [1]. While a thorough and rigorous application process is necessary, and should be expected out of the relevant regulatory bodies, many wanted to know how it could be streamlined. Understandably, this was a challenging question that will require many other discussions to address. In the meantime, attendees were encouraged to familiarise themselves with Health Sciences Authority’s (HSA) Clinical Trials Regulatory Guidance, which outlines the regulatory roadmap for clinical trials. It includes the processing timelines that may be helpful for planning. There was also a call for individuals to spearhead new initiatives to support the development of the local clinical trial landscape as it matures even more. If you have any ideas, share it with SCRP!

High cost of clinical trials in Singapore – what’s included in the package?

Singaporeans are known for our pragmatism, which may explain why many of the questions asked by the attendees surrounded the cost of running clinical trials. After all, what would justify a high cost [100M USD pumped into clinical research in 2015: 2]? We covered Singapore’s unique ecosystem in our Oct 2023 issue, but this uniqueness becomes especially relevant when an expensive and multi-stakeholder endeavour is in consideration. A close-knit community means resources are immediately more accessible; here, we may not be separated by six degrees of separation, but five, or four, even. While Singapore’s small population puts it at a disadvantage for clinical trials since they often require large numbers of observations, the panellists argued that Singapore’s upper hand lies in its efficiency, “we can recruit faster [so] we can begin faster”. This efficiency is the result of many favourable factors and a strong infrastructure, which streamlines the processes at every critical point. Therefore, high quality comes with a high cost, and the audience was urged to think about cost relative to what’s in the package.

The Straits Times wrote a commentary on the importance of running local research trials despite being small in 2023
TecEx Medical summaries the advantages and disadvantages of Singapore as a destination for clinical trials
We thought Huren Sivaraj’s essay on the local cancer clinical trial landscape was good

Know a friend who’d enjoy learning about the local biotech scene?

Digital therapeutics are relatively new – where are we in terms of clinical trials?

Very much a part of popular (and academic) culture, AI is now integrated into many biologists’ inquiry into a gene or a protein (think AlphaFold2). However, despite the tremendous development being made in AI research and technology, there is an non-equivalent development made in implementation of AI. In fact, from 2010 to 2022, there were a total of only 31 clinical trials being conducted related to digital therapeutics (DTx) worldwide, and only increasing in the recent years (3: Figure 1) – yes, to be qualified as a therapeutic, DTx must be clinically validated, too! Furthermore, DTx was only defined in 2015 (less than a decade ago!), which adds to the ambiguity of such therapeutics, and its regulation in the market. Currently, there appears to be no international consensus on a regulatory model for DTx [3], although testing modalities and digital clinical endpoints have been identified [4]. Interestingly, it was commented that there is a tendency to reduce the field of AI into pattern-finding in big datasets for diagnoses (and it is this – it’s just not just this), hence attendees were encouraged to understand that not all AI is the same. Panellists added that the use of AI should be more intentional, prompting the question, “Do you need AI to do this?”, which we think could be a critical question to be asked whenever we want to employ AI.

Get a copy of Prof Dean Ho’s book on Digital Therapeutics

^Drawn by sandserif

Through the panel discussion, we were impressed by how the people gathered and rallied, how each comment or question was imbued with a sense of drive and responsibility; they understood the role they played in contributing to the development of the space. While these authors have not worked on clinical research (Kimwhye does mechanobiology, Liyana does bacterial genetics), we left the panel with a greater appreciation for the complexities of clinical trial design and coordination, along with associations for providing the platform for issues to be raised and discussed- kind of like us with a different focus!

🎧 Nucleate Singapore Pulse

Screening diseases through pharmacogenomics with NalaGenetics’ Levana Sani

This month, we interviewed Levana Sani, Co-founder and CEO of NalaGenetics. Levana and her team founded Nalagenetics with the mission to democratise access to genetic testing tailored to the unique genetic make-up of the Southeast Asian population. She also highlights the differences in commercialisation in Singapore and Indonesia, and the current challenges faced with the adoption and application of pharmacogenomics in clinics.

View show notes and transcript

Listen now

📆 Events happening this month

Conference/Forum

Biologics Manufacturing Asia 2024 | IMAPAC
(20 Mar, 8:00 AM - 21 Mar, 6:00 PM, in person at Singapore 018956)
Clinical Trials Festival Asia 2024 | IMAPAC
(20 Mar, 8:00 AM - 21 Mar, 6:00 PM, in person at Singapore 018956)
Asia Bio Partnering Forum | EDB
(24 Apr - 25 Apr, in person at Singapore 018956)
(29 Apr - 30 Apr, virtual)

Ask your friends along a biotech event this coming month.