Antibody and Product Development

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.

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.

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.

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

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.

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.

Antibodies


• Ling WL, Lua WH, Gan SKE (2020) Sagacity in Antibody humanization for therapeutics, diagnostics and research purposes: Considerations of antibody elements and their roles Antibody Therapeutics, 18 April 2020. tbaa005, https://doi.org/10.1093/abt/tbaa005.


• Samsudin F, Yeo JY, Gan SKE*, PJ Bond* (2020) Not all therapeutic antibody isotypes are equal: the case of IgM versus IgG in Pertuzumab and Trastuzumab. Chemical Science. 12 February 2020, 11, 2843 – 2854. DOI: 10.1039/c9sc04722k. * Joint corresponding.


• Lua WH*, Su CTT*. Yeo JY, Poh JJ, Ling WL, Phua SX, Gan SKE. (2019) Role of the IgE variable heavy chain in FcεRIα and superantigen binding in allergy and immunotherapy.Journal of Allergy and Clinical Immunology. Aug 2019;144(2):514-523.e5. doi: 10.1016/j.jaci.2019.03.028. Selected for Editor’s Pick August 2019.


• Ling WL, Lua WH, Poh JJ, Yeo JY, Lane DP, Gan SKE (2018). Effect of VH-VL families in Pertuzumab and Trastuzumab recombinant production, Her2 and FcgIIA-binding. Frontiers in Immunology. Mar 12, 2018, 9:469 doi: 10.3389/fimmu.2018.00469. 4 "Isotype" Sci Rep 2018


• Lua WH, Ling WL, Yeo JY, Poh JJ, Lane DP, Gan SKE. (2018) The effects of Antibody Engineering CH and CL in Trastuzumab and Pertuzumab recombinant models: Impact on antibody production and antigen-binding. Scientific Reports, 15 January 2018. 8:718 doi: 10.1038/s41598-017-18892-9 . Author correction of accession numbers made 18 July 2018.


• Su CTTC*, Ling WL*, Lua WH, Poh JJ, Gan SKE. (2017) The role of Antibody Vκ Framework 3 region towards Antigen binding: serendipitous effects on recombinant production and Protein L binding. Scientific Reports, 19 June 2017 7: 3766 doi: 10.1038/s41598-017-02756-3.

Virus


• Yeo JY, Goh GR, Su CT, Gan SKE (2020) The Determination of HIV-1 RT Mutation Rate, Its Possible Allosteric Effects, and Its Implications on Drug Resistance. Viruses 27 March 2020, 12(3), 297. DOI: 10.3390/v12030297.


• Su C.TT, Koh DWS, Gan SKE.(2019). Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs. Molecules. 6 September 2019, 24(18), 3243; doi: 10.3390/molecules24183243.


• Su CTTC, Kwoh CK, Verma CS, Gan SKE. (2017) Modeling the full length HIV-1 Gag polyprotein reveals the role of its p6 subunit in viral maturation and the effect of non-cleavage site mutations in protease drug resistance.v Journal of Biomolecular Structure & Dynamics. 27 December 2017: 1-12. Doi: 10.1080/07391102.2017.1417160.


• Chiang RZH, Gan SKE, Su CTT. (2018). A computational study for rational HIV-1 non-nucleoside Reverse Transcriptase inhibitor selection and the discovery of novel allosteric pockets for inhibitor design. Bioscience Reports. 05 March 2018, 38 (2) doi:10.1042/BSR20171113 Doi: 10.1042/BSR20171113. 5 InCob paper

Apps & Devices


• Su CTTC, Kwoh CK, Verma CS, Gan SKE. (2017) Modeling the full length HIV-1 Gag polyprotein reveals the role of its p6 subunit in viral maturation and the effect of non-cleavage site mutations in protease drug resistance. Journal of Biomolecular Structure & Dynamics. 27 December 2017: 1-12. Doi: 10.1080/07391102.2017.1417160.


• Sim JZ, Nguyen PV, Zang Y, Leow MKS. Gan SKE. (2017) Thyroid-SPOT: Thyroid treatment management app. Scientific Phone Apps and Mobile Devices. 30 August 2017, 3: 4, doi: 10.1186/s41070-017-0016-y. Sim JZ, Nguyen PV, Gan SKE, Leow MKS. Thyroid-SPOT for Android and iOS - Invention filed May 2015 SICS/Z/09136.


• Ng KM, Wong CF, Liang AX, Liew YH, Yeo JY, Lua WH, Qian XJ, Gan SKE (2017) APD SpectBT: Arduino-based mobile vis-Spectrophotometer.Nature Methods Application Notes. March 14 2017 doi:10.1038/an9827.


• Nguyen PV, Ghezal A, Hsueh YC, Boudier T, Gan SKE*, Lee HK* (2016). Optimal processing for gel electrophoresis images: Applying Monte Carlo Tree Search in GelApp. Electrophoresis. 2 June 2016, 37, 2208–2216, doi: 1.1002/elps.201600197. *Joint corresponding. 3 Skin monitoring app


• Gan SKE, Poon JK (2016) The World of Biomedical Apps: their uses, limitations, and potential. Scientific Phone Apps and Mobile Devices. 19 July 2016, 2:6. doi: 10.1186/s41070-016-0009-2


• Nguyen PV, Verma CS, Gan SKE. (2014) DNAApp: a mobile application for sequencing data analysis. Bioinformatics. 5 August 2014 ;30(22):3270-1 doi:10.1093/bioinformatics/btu525.Tech disclosure filed Mar 2014: BII/Z/08384; Covered in over 80 news agencies worldwide, including Nasdaq, Yahoo Finance, Bloomberg, Life Scientist, etc; . *Corresponding author. 1st in Top 10 apps for busy researchers (Biotechniques 2014).

Psycho & others


• Phua SX, Chan KF, Su CTT, Gan SKE (2019). Perspective: The promises of a holistic view of proteins - impact on antibody engineering and drug discovery.Bioscience Reports. 30 Jan 2019, 39 (1). doi:10.1042/BSR20181958


• Goh BYL, Yeo JYY, Gan SKE (2019). Psycho-otorhinomicrobiology: The link between the flora of the nose and ears and that of the psyche. APD Trove. 25 March 2019; 2:2. doi: 10.30943/2019/25032019.


• Ng RYX, Wong YS, Koh CLZ, CW, Yeo JY, Gan SKE (2018). The Associations between Dietary Practices and Dietary Quality, Biological Health Indicators, Perceived Stress, Religiosity, Culture, and Gender in Multi-Cultural Singapore. Journal of Ethnic Foods. 29 July 2018. Vol 5: 220-227. Doi: 10.1016/j.jef.2018.07.003.


• Chew ASQ, Yu YT, Chua SW, Gan SKE.(2016) The effects of familiarity and language of background music on working memory and language tasks in Singapore. Psychology of Music. 21 March 2016; Vol 44 (6): 1431–1438. doi: 10.1177/0305735616636209.


• Gan SKE, Lim MJ, Haw YX. (2015) The Relaxation Effects of Stimulative and Sedative Music on Mathematics Anxiety: A Perception to Physiology Model. Psychology of Music. 19 June 2015; 44(4): 730–741. doi:10.1177/0305735615590430.



• View full list of publications here