Antibody and Product Development

BII - Antibody and Product Development Group Photo

Research

Antibody & Product Development (APD) Lab Group is a Singaporean lab doing research for Singapore and Singaporeans in mind set up in Oct 2013 with support from Sir David Lane and from BSF (now called Research Support Services). Our multi disciplinary work spans across molecular cell biology, computer science, biomolecular modelling, psychology, IoT, scientific phone apps, augmented reality, and psychology. We are unique in possibly being the only lab in the world with reasonable achievements in the various disciplines simultaneously, all within the short six years or so (see facebook.com/APDLab and twitter.com/DrSamuelGan), We demonstrate our own capabilities through our own efforts in ethical scientific publishing and research practices, providing scientific services and even attracted overseas drug developers for validation! Our work in antibody engineering and drug design is summarised in our perspective article (Phua et al., 2018) and our post-doc Dr Su was also recognized for her work sufficiently to be invited for journal submissions (Su et al., 2019). See https://www.facebook.com/APDLab/videos/336377246957654/ for our work on drug design using HIV as a model. We have to date > S$5M of grants, of which ~ S$4M comes directly to us.

Achievements
Since 2013, we produced >70 publications from our own research, where APD folks are first and/or corresponding authors. We trained -80 interns from local institutions, graduated ~ 40 degree project students in Biomed Eng, Psych, Biomed, and developed ~50 products (including apps, Google Play Store – APD Lab or Apple App Store – Samuel Gan). We were highlighted in media world-wide hundreds of times, including by Frost & Sullivan, Bloomberg, Yahoo Finance, etc. We are also home to the first and only specialized “Scientific Phone Apps and Mobile Devices” journal in the area, as well as the neutral multi-level, multi-disciplinary open-access student journal “APD Trove”. On average, we have a paper and intern trained per month! No one can say truthfully that we leeched off anyone for our publications or training.

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Figure 1:  Full List of our Apps

Therapeutic Antibody Engineering
Antibodies were once again in the spotlight in 2018 because of the Nobel Prize award to Prof Sir Greg Winter for the ingenious Phage display method. 

In this effort, we not only found great promise in localizing antibodies by changing the constant region of the heavy chain, but also that it is possible to fine-tune antigen and Ig receptor engagement by manipulating distal elements (Figure 2). Beyond this, we have further investigated the Ig-IgR interaction for possible interventions and as a proof-of-concept (Figure 3), allosteric epitopes as well as small molecule inhibitors are also possible. At this point of writing, we have many potential small molecule inhibitors against the IgE-FcεRI interaction for further investigations. 

All together, these findings open up new opportunities where a holistic approach to antibodies can result in better therapeutics. Our ongoing work investigates the impact of such findings to improve the “magic bullet” suggested by Paul Ehrlich as well as a supply for potential interventions for pathologies.

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Figure 2:  The elements in the whole antibody can elicit distal effects on important functions such as antigen and Ig receptor binding.
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Figure 3: Allosteric epitope analysis of IgE high affinity receptor provides possible interventions against the interaction necessary for Type 1 Hypersensitivity.

2019 saw our highest impact publication (and easily one of the highest impact factor research article from a single lab in the history of the institute) in the top journal of Allergy - “Journal of Allergy and Clinical Immunology” at IF 14.110 and as Editor’s pick for the issue. Late 2019, our method for a holistic view of the immune system was published in the classical “Journal of Immunological Methods”. What better recognition of our work on antibodies, allergy and immunology than being in the right journals of the field where discernment abounded! 


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Grooming Local Talent and Start-Ups
As a lab funded via the government agency, what better way to invest Singapore taxpayer money than on grooming young Singaporeans? We groomed local talent from scratch (nobody can truthfully say we poached any one) with a lab team of all locals with the exception of our post-doc trained in NTU, and our software engineer from Temasek Polytechnic serving her tuition grant bond to Singapore. Every one of our staff had contributed significantly to the lab’s notable research output and many who joined us in 2013/4continue to be productive scientists in their own right with us. Even our interns walked away with a publication/product from their short stint, outperforming many PhD holders (just refer to our annual publication list). Notable examples include Mr Joshua Yeo with 8 publications; Mr Phua Ser Xian with 4 first-author publications; Mr Ron Chiang with a first-author paper; Mr Sim JZ who made >7 mobile apps with publications. The list goes on to >70 interns! We even have publications that the PI willingly let the students publish on their own for their own credit. Clearly, with our allocated research budget, we punched above our weight significantly. We even attracted an Asst Prof to express interest in joining APD Lab as a visiting scientist!

On Local Industry

Working with RSC A*STAR, we supported no less than five local companies, and are working towards formal support to the local community via Enterprise Singapore and SERC. We are the only lab in BII to do so, and are in the midst of preparing potential spinoffs from our work.

Social Impact and STEM Education in Singapore
Although A*STAR’s mandate is not in education. APD Lab is the home to three courses, two of which are SkillsFuture accredited! All from a small team of 8 of only one post-doc!

  • “Introduction to Bioinformatics with Scientific Phone Apps” with TP
  • “Specialist Diploma in biomedical informatics” jointly offered by RP and NP.
  • “Certificate in Next-Gen Sequencing” with NP
  • “Experimental Biomedical Laboratory Skills” with SUSS
  • “Advanced Experimental Biomedical Laboratory” with SUSS

We also supported Cardiff Metropolitan University (CMU) & Dimensions International College BSc and MSc lab modules.

Scientific Apps, IoT, AR and Psychology Game Apps
Apps: https://www.facebook.com/watch/?v=809326746096334
Psychology: https://www.facebook.com/watch/?v=2260548674189109 

As one of the pioneering scientific app labs in the world, we setup our own makerspace also available as a service, while continuing our work in psychological well-being of Singaporeans. We even signed a MOU with Schulke & Mayr (Asia) to use our APD Skin Monitoring App for clinical trials beyond Singapore’s shores in Penang.

Combining both smartphones and devices, we created leisure apps for socializing and wrist exercises; used our 3D printer for solutions for the aged; monitoring of pressure points on feet; incorporated augmented reality (AR) via apps, all with support from our own startup APD SKEG Pte Ltd.

HIV Drug Resistance and Drug Therapy
Our research into HIV drug resistance has bought us to model HIV-1 Gag (Figure 4), and computational analysis based guidance to drug selection for delaying drug resistance. While we previously applied such drug resistance computational analysis to HIV Protease (Su et al., 2016), we further applied this to HIV-1 Reverse Transcriptase. Given the small selection of clinical non-nucleoside RT inhibitors (nnRTIs), we further looked for novel allosteric druggable pockets and found three (Figure 5). Leveraging on our in vitro capabilities, we performed experiments and found three small molecules that showed inhibitory activity. These molecules are undergoing publication write-up and also attempts to put through the drug development pipeline.

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Figure 4:  
Full model of Gag revealed the possible conformational changes during HIV-1 maturation.

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Figure 5:  Structural and allosteric analyses of HIV-1 RT reveals new druggable pockets that we have found promising in vitro tested inhibitors.

New Areas of Research and Solutions for Singapore, Singaporeans and Science

Contributing solutions for Singapore with the help of poly graduate Mr Darius Koh (who illustrated the below figure), an intern to be hired as staff, we started research on plastic degradation for our proposal of DE-SCRAP (Developing Environmental Biotechnology – Singapore Carbon Recycling and Accelerated Plastic bioremediation) together with local companies and polytechnics.

Within A*STAR, we provided IT solutions for grant office operations, creating three software to add in grant review (A* Review Assistance System or A*RAS), auditing of grant items (A*Grant Audit Flagging Systems or A*GAFS), and also in capability mapping and searching for expertise (A* Capability & Expertise Search or A*CES), all created by local poly interns and help from our staff. This demonstrates our ability as an innovation center to solve problems in a cost-effective way, while grooming the future of Singapore.

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Figure 6: Illustration by one of APD Lab's intern. 

Outlook for 2020

APD is a go-getting highly independent lab that grew scratch with mostly fresh graduates to an established lab with ~70 publications all from the lab itself, carving our way in multiple disciplines simultaneously, setting up courses with local institutions, training many students, and starting new research areas. It is almost unbelievable that the lab had only one post-doc. In late 2019, Dr Gan was featured in a book “Innovation through Fusion” ISBN: 9781547401543 written by Dr CJ Meadow of SP Jain School of Global Management, Innovation & Insights Center as one of 30 world-class innovators for his multi-disciplinary work demonstrating that home-grown Singaporean scientists are among world-class innovators.

APD Services

Staff involved: Mr Poh Jun Jie, Mr Ling Wei Li, Mr Chan Kwok Fong.

APD Services are provided through A*STAR Research Support Centre (RSC). Our biomedical services include:

  • Biomedical laboratory workshop and course development;
  • Customized scientific services such as molecular cloning, protein production and purification;
  • Computational biology analysis;
  • Mycoplasma testing;
  • Antibody engineering;
  • 3D Printing;
  • scientific app development; and
  • Other customized services.

Our technical services are unique in that they are provided by publishing researchers that use the very same research methods, technology, and equipment for our everyday research. Leveraging on the scientific success of APD Lab as evidenced from the publications, APD services are performed at publishable research quality.

In our offering of customized scientific services and antibody engineering, we leveraged on our own research findings and published work, such that we have been approached by overseas biosimilar companies for validation testings. Our mycoplasma and now defunct endotoxin services have also supported local small medium enterprises (SMEs) involved in clinical trials.

Our track record includes both local and overseas SMEs and multi-national companies (MNCs), as well as local educational institutions:

  • Endotoxin and mycoplasma testing for local SME clinical trials
  • Antibody engineering for other A*STAR research entities
  • Customized molecular cloning and protein engineering for MNCs and other A*STAR research entities,
  • 3D Printing for internal A*STAR event.
  • Workshop support for local SMEs/MNCs
  • Biomedical laboratory training for local educational institutions MSc courses.
  • Course development of Biomedical lab skills for BEng for SUSS.
  • App development for another A*STAR research entity
  • Lab-based event support for local SME/MNC.
  • Joint Bioinformatics course development with local polytechnics.
  • And many others.

As APD Services continue to grow, we hope APD Services could be a model towards sustainable biomedical research.

Click here to find out more on the applications produced by this group. Panel of apps released by APD Lab can be found on the Google Play and Apple Store.

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Figure 1: 3D Printed trophies for the A*AI Hackathon 2018.
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Figure 2: Lab workshop featured in Straits Times article, based on the development and running of biomedical experimental skills modules with Singapore University of Social Sciences.
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Figure 3:  Bioinformatics Workshop development with Temasek Polytechnic in 2017.

Members

 Senior Principal Investigator  GAN Samuel   |    [View Bio]  
 Research Scientist  SU Tran To Chinh 
 Research Officer CHAN Kwok Fong
 Research Officer LING Wei Ling
 Senior Laboratory Officer  POH Jun Jie
 Laboratory Officer KOH Wen Shou Darius 
 Laboratory Officer YEO Yi Joshua
 Software Technician WU Weiling

Selected Publications