ISAJ Newsletter - Volume 4, Issue 2 (December 2019)

From the Editor’s Desk

Greetings and a warm welcome on the second issue of ISAJ Newsletter for 2019! We take this opportunity to convey the seasonal greetings for coming festive season. May happiness and prosperity fill your life forever!

In this issue, we present three diverse articles. Two of them briefly summarize research work on track monitoring and anti-cancer treatment, while the third article recaps the experience at Gap Summit 2019 hosted at Broad Institute of MIT & Harvard, Boston.

We take pleasure in informing that our 10th ISAJ annual symposium on “Interdisciplinary Science and Technology Innovation for Sustainable Society” was held on December 9, 2019 at Osaka University Hall, Toyonaka Campus. The event commemorated the 10th anniversary of ISAJ. H.E. Mr. Sanjay Kumar Verma, Ambassador of India to Japan inaugurated the symposium and Mr. B. Shyam, Consul General of India Osaka-Kobe delivered a special lecture. The symposium was attended by approximately 60 Indian and Japanese researchers.

Event Report: Gap Summit 2019 - Global Biotech Revolution

By Ankita Jain, Business Development Associate, Healios K.K.

I was selected as one of the 100 Leaders of Tomorrow by Global Biotech Revolution (GBR) for the world-class biotechnology leadership summit held June 16-20, 2019 at Kendall Square, Cambridge, MA.

Summit Themes and Challenges

The aim of the Gap summit is to bring together different stakeholders ranging from academia to industry and from NGOs to international organizations, to discuss and solve the different ‘gaps’ in the global biotech ecosystem. Themes for this year revolved around:

1. R&D Productivity: Reducing high failure rates in pharmaceutical product development
2. Bench to Market: Making technology transfer a more seamless process
3. AI & Digital Health: Impact of deep-tech penetration in biotech industry
4. Biosecurity & Bioethics: Incentivizing stakeholders for global policy making
5. Sustainable Healthcare Economics: Providing accessible healthcare with aging populations
6. Sustainability & Agri-Tech: Biotech solutions for feeding growing populations
7. Global Bioeconomies: Democratizing the biotechnology industry

Key Highlights

The 5-day summit kicked off with introductory remarks by Dr. Tedros Adhanom, Director General, World Health Organization. This was followed by panel discussions featuring representatives from:

• Leading pharma companies: Novartis, Biogen, Bayer
• Global organizations: World Bank, Bill & Melinda Gates Foundation
• Eminent academicians: Prof. Phillip Sharp, Nobel Laureate, MIT

Bio-Innovation Competition

The 100 Leaders participated in a 4-month long Bio-Innovation Competition. I collaborated with 4 other leaders from Denmark, UK & US. Under mentorship from Johnson & Johnson R&D leaders, we developed a digital solution for providing first-line screening for women’s fertility health. Selected teams received initial seed-funding and mentorship to build biotech startups.

Key Takeaways

Convergence, Consensus & Coordination - More interdisciplinary teams will be needed to collaborate and co-develop innovative solutions for addressing both present and future challenges.

Applications for Gap Summit 2020 are open at www.gapsummit.com/apply/

From the Pen of Young Mind: Combination Immunotherapy Using Synthetic Genetic Switches

By Madhu Malinee, Kyoto University

Cancer is the second most leading cause of deaths worldwide. The number of new cancer cases per year is expected to rise to 23.6 million by 2030. While chemotherapy is the most preferred treatment, toxic side effects and resistance warrant alternative strategies.

The Challenge

The interaction of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) causes T cell inhibition, thereby inhibiting anti-tumor immunity. U.S. FDA has approved anti-PD-1 or anti-PD-L1 antibodies for many cancers. However, the high cost of PD-1 blockade therapy (approx. USD $1M per patient per year) restricts its worldwide application, considering 70% of cancer patients are from developing countries.

Our Innovation

We have developed designer PIPs (N-Methylpyrrole and N-methylimidazole hairpin polyamides) as a cost-effective combinatorial approach:

1. Genetic OFF Switches: Chb-PIP conjugate to ‘Switch OFF’ PD-L1 expression in cancer cells
2. Genetic ON Switches: PIPs conjugated with epigenetic activator CTB to induce transcription factors for mitochondrial activation

Results

We synthesized Chb-PIPs that selectively switch OFF PD-L1 gene expression:

• PD-L1 expression inhibited at transcript level (qPCR analysis)
• PD-L1 suppression confirmed at protein level (flow cytometry)
• Currently screening PIPs for upregulation of mitochondrial biogenesis mediated by PGC-1α

These initial findings pave the way for development of cost-effective PD-1 blockade therapy to benefit more cancer patients globally.

Research Spotlight: Response Based Track Profile Estimation Using Observable Train Models

By Dr. T. Jothi Saravanan, JSPS Postdoctoral Fellow, Yokohama National University

Local railway networks suffer from age-related deterioration and poor maintenance. Track profile, which directly influences ride quality and safety, needs to be estimated for maintenance purposes.

Current Challenges

Currently, Track Recording Vehicles (TRV) such as Doctor Yellow in Japan are utilized for track condition monitoring. However, TRVs are:

• Expensive to operate
• Cannot be frequently used for local railway lines
• Used only once a year for most lines

Proposed Solution

We have developed a robust inverse analysis scheme for track geometry estimation from local in-service train responses:

1. Extended Augmented State Kalman Filter (ASKF): Solved the Observability Rank Condition for state space model
2. Sensor Optimization: Theoretically obtained appropriate sensor types and placements
3. Multi-Body Simulations: Used SIMPACK to investigate different factors and validate algorithm

Key Achievements

• Vertical Track Profile: Good agreement for straight track sections
• Lateral Track Profile: Can estimate wavelengths above 8m
• Practical Implementation: Uses accelerometer and gyroscope mounted on car body floor and bogie mass
• Validation: Tested on experimental measurements from in-service local railway lines

Impact

This system provides:

• Cost-effective alternative to expensive TRVs
• More frequent monitoring capability
• Real-time track condition assessment
• Enhanced safety for local railway networks

The proposed approach enables efficient and frequent track monitoring using regular in-service trains, potentially transforming railway maintenance practices.

10th Anniversary Symposium

The 10th ISAJ Annual Symposium on “Interdisciplinary Science and Technology Innovation for Sustainable Society” was successfully held on December 9, 2019 at Osaka University Hall. This milestone event commemorated ISAJ’s decade of fostering India-Japan scientific collaboration.