Antibody and Product Development

Samuel K.E GAN
Principal Investigator

SU Tran To Chinh Senior Post Doc Research Fellow

LUA Wai Heng Research Manager

CHAN Kwok Fong, LING Wei Li, CHOO Jun Keat, Bryan Research Officers

POH Jun Jie Laboratory Officer

WU Weiling Software Technician

Antibody & Product Development (APD) Lab Group was officially set up in Oct 2013. Working closely with other entities in and beyond A*STAR (including local SMEs), the interdisciplinary nature of streams spans across molecular cell biology, computer science, complexity sciences, biomolecular modelling, psychology, IoT, scientific phone apps, augmented reality, and psychology game development. The uniqueness of the lab is that it not only works in, but has also made reasonable achievements in the various multiple disciplines. Our academic successes have also allowed us to provide services to the local scientific community and beyond – see APD Services tab.

*Please view the augmented reality animations, view the pictures of this page using the APD AR Holistic Review App, available from the Apple and Android app stores.

Achievements

Since inception in 2013, APD lab has produced more than 60 publications (including research articles, books, technology disclosures, etc), all from our own research, where APD folks are first and/or corresponding authors. We have trained more than 60 interns from polytechnics and universities, graduated more than 20 final year degree project students, and developed more than 50 products (for our apps, see Figure 1). Our work has been highlighted in news and magazines world-wide over hundreds of times, including by Frost & Sullivan, Bloomberg, Yahoo Finance, etc. APD lab is also the home lab to the first and only specialized journal "Scientific Phone Apps and Mobile Devices" in the area of apps and IoT, as well as the neutral open-access student journal "APD Trove".

Given our publications and trained interns, we have essentially almost an average of a paper and intern trained per month!

2018 had been a very interesting year for us. We had the highest numbers of publications (> 12, the number of months in a year!), branched into IoT devices and released our record number of mobile apps released in one year, along with our record number of overseas talks that include: Seoul Allergy Congress, BioCon 2018 Shanghai, Interstellar Initiative in New York, Antibody Symposium, etc. At the end of 2018, we also had promising preliminary results of possible drug candidates against HIV-RT and IgE-FcεRI. There is much to look forward to what 2019 will bring us!

Scientific Apps, IoT, AR and Psychology game apps

As one of the pioneering labs in the world to work on on scientific apps, we have branched into IoT devices and 3D printing in 2018. We have also begun to incorporate augmented reality (AR) via apps into our publications and scientific communications. Through an intensive learning programme, we ventured into Arduino and Micro:bit to build prototype devices and also leveraged on 3D printing technology to complement our research work. We combined our efforts in AR and psychology towards the development of game apps that could be utilized for our psychological research (e.g. APD Recollection, APD Misdirection, and APD Labyrinth game apps). Many of these efforts are in various stages of commercialization as well as for publications and grant applications for 2019.

Figure 1
Figure 1: Apps released by APD Lab since 2014. Game apps shown separately: APD Shakestra and APD Recollection (right).

Therapeutic Antibody Engineering

In 2013, APD Lab was started on a large grant on antibody engineering. In the course of this area of research, we have published no less than 8 papers (4 in 2018 alone) since, detailing how antibodies and antibody receptors can be engineered to have better therapeutic effects. 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.

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

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 toxicity tests at the moment, and preliminary results suggested these molecules to be safe with no cross reactivity with other proteins apart from the viral RT. On-going work to further verify and develop these potential inhibitors are ongoing.

Figure 4
Figure 4: Full model of Gag revealed the possible conformational changes during HIV-1 maturation.
Figure 3
Figure 5: Structural and allosteric analyses of HIV-1 RT reveals new druggable pockets that we have found promising in vitro tested inhibitors.

Future Work

With potential applications to develop better therapeutic antibodies and to intervene in the pathology of Type I Hypersensitivities and HIV, there is much to do. Simultaneously, prototype devices which were built would also be further developed. There is scope to apply our platform for antibody engineering towards a wide range of therapeutic antibodies that includes viral/bacterial/autoimmune diseases. On the area of allosteric pockets and druggable sites (work with Berezovsky group), our proof-of-concept in FcεRI and HIV-RT showed the ease of such application to both existing and new drug targets.

An exciting result from our merging of psychology, biomedical sciences, and smartphone apps can be seen in our psychology game apps. Given the ripening of many of our research streams, further combination of these streams will certainly build more niche areas for APD.

Conclusion

Although a young lab of just over five years old, APD Lab has diversified its research areas and showed independent achievements in these areas, predominantly funded by competitive funding over this time. APD Lab does not take things for granted, acknowledging the responsibility to make a positive impact. We rely heavily on our staff and the every flowing flux of interns that contribute to the over 50 publications, apps, and other achievements we have today. And we show this appreciation of our staff and interns in that APD Lab is almost never referred to as anything else but as APD, and also the fact our publications include those that are without the Principal Investigator, where staff and even interns are corresponding authors.

The focus of the lab remains to make a positive impact on society in people development and all the research areas that we work in. With many of our research coming to fruit, such as our antibody and inhibitor efforts, our team effort involving not just the staff, but also the interns, put APD Lab in a good position to make this impact.

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: 1) Biomedical laboratory workshop and course development; 2) Customized scientific services such as molecular cloning, protein production and purification; 3) Computational biology analysis; 4) Mycoplasma testing; 5) Antibody engineering; 6) 3D Printing; 7) scientific app development; and 8) 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:

  1. Endotoxin and mycoplasma testing for local SME clinical trials
  2. Antibody engineering for other A*STAR research entities
  3. Customized molecular cloning and protein engineering for MNCs and other A*STAR research entities,
  4. 3D Printing for internal A*STAR event.
  5. Workshop support for local SMEs/MNCs
  6. Biomedical laboratory training for local educational institutions MSc courses.
  7. Course development of Biomedical lab skills for BEng for SUSS.
  8. App development for another A*STAR research entity
  9. Lab-based event support for local SME/MNC.
  10. Joint Bioinformatics course development with local polytechnics.
  11. And many others.

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

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.

Antibody and Product Development Members

Dr. Samuel K.E GAN
Principal Investigator
 
  Biography Details
NameTitle
Dr. GAN SamuelPrincipal Investigator
Dr. SU Tran To ChinhPostdoctoral Fellow
Mr. LUA Wai HengResearch Manager
Mr. CHOO Jun Keat BryanResearch Officer
Mr. CHAN Kwok FongResearch Officer
Mr. LING Wei LiResearch Officer
Ms. WU WeilingSoftware Technician
Mr. POH Jun JieLaboratory Officer

This section is still work in progress.