Education＆ScienceResearch fund opportunities

Planned, current and past projects

1. 2024-2025

   Investigation and development of a broad spectrum anti-viral therapy for both seasonal and pandemic influenza A viral infections

   Principal Investigator:

   Dr Alan Chen-Yu Hsu (Singapore)

   Co-Investigators:

   Dr Jemma Mayall (Australia)
   Dr Jay Horvat (Australia)
   Dr Kai Sen Tan (Singapore)
   Dr Peter Wark (Australia)

   Project term

   1 January 2024 – 31 December 2025

   Project Summary

   Background

   Iron is essential for many biological processes. To maintain tissue homeostasis, iron levels are tightly regulated by systems that control iron absorption, systemic transport and cellular uptake, storage, and release. Loss of iron homeostasis in either direction leads to cellular dysfunction and pathognomonic changes. It is well established that, to survive and replicate, pathogenic bacteria have evolved strategies to source host iron and to counter these microbial strategies, host organisms have evolved immune-mediated mechanisms that reduce iron availability to pathogens, particularly at mucosal sites, which are frequently the front line of defence. More recently, links have been reported between iron levels and metabolism and the severity of viral infections. However, it is currently unknown if respiratory viral infections alter iron metabolism, or if altered iron metabolism or availability in the cells and tissues of the respiratory tract directly increase susceptibility to infections or resultant disease.

   Innovative approach

   By combining new applications of unique tools, interventions, and models, and collaborations with world-leading experts in respiratory immunobiology, iron biology, and respiratory viral infection, this team has established a collaborative research program between Singapore and Australia to:
   Investigate how seasonal and potentially pandemic influenza A virus (IAV) infections affect host iron metabolism and whether iron metabolism can be therapeutically targeted for the treatment of both seasonal and potentially pandemic IAV infection and infection-induced disease.
   We have collected world-first pilot data to show that influenza A virus (IAV) infection alters iron metabolism in the airways and systemically, and that iron levels and iron-related metabolic processes play a crucial role in host defence, and in determining IAV-induced disease outcomes. We show that iron uptake processes are down-regulated in whole lung and airway epithelial cells (AECs) during IAV infection. Significantly, increased iron levels in AECs increase IAV replication. Most importantly we show that depleting transferrin receptor 1 (TFR1)-mediated cellular iron uptake in the airways reduces viral load and protects against IAV-induced disease in in vivo mouse model of IAV infection.
   This APSR Multi-Society Research Project will extend upon these preliminary data to determine, for the first time, how seasonal and potentially pandemic IAV infections affect iron metabolism and validate the efficacy of TFR1-targeting therapies for the treatment of seasonal and potentially pandemic IAV infections and pathology in primary human airway epithelial cells cultured at the air-liquid interface.

   Hypotheses

   Both seasonal and potentially pandemic IAV infections induce changes in iron metabolism in airways cells. These responses alter iron availability, modulate cell function and play an important role in determining the pathological outcomes of respiratory viral infection. Targeting these processes can be used to treat IAV infections and their devastating effects.
   To address these hypotheses, this APSR grant will:
   Aim 1. Comprehensively characterise how seasonal and potentially pandemic IAV infections affect iron metabolism in fully differentiated human airway epithelial cells.
   Aim 2. Determine if targeting iron metabolism therapeutically, influences host defence and IAV-induced pathology.

2. 2023-2024

   Validation of soluble programmed death-1 in predicting progression of nodular-bronchiectatic form of nontuberculous mycobacterial lung disease: a Multi-Country Research

   Principal Investigator:

   Dr Chin-Chung Shu (Taiwan)

   Co-Investigators:

   Dr Kozo Morimoto (Japan)
   Dr Sheng-Wei Pan (Taiwan)
   Dr Jae-Joon Yim (Republic of Korea)
   Dr Yao-Wen Kuo (Taiwan)

   Project term

   1 January 2023 – 31 December 2024

   Project Summary

   The incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide and in Eastern Asia. NTM-LD leads significant morbidity and mortality, around 25% within 5 years, but the treatment rate is low because the course of NTM-LD is indolent, especially in nodular-bronchiectatic (NB) form. However, there is no biomarker proven for predicting the progression in NB form of NTM-LD.
   Recently, it has been reported that the ratio of membrane-form programmed death-1 (PD-1) expressed T cells increased in patients with NTM-LD and it was associated with disease severity and progression. The mechanism has been speculated as a “immune exhaustion”. In contrast to PD-1 expressed in cell membrane, soluble-form PD-1 is another biomarker that can be easily detected in blood. We recently reported that soluble PD-1 significantly correlated with cavitary lesion and disease progression in patients with NB-form NTM-LD in Taiwan. However, this has not been validated in other countries.
   Therefore, we will conduct this project to investigate the role of soluble PD-1 in NB-form NTM-LD through a multi-country cooperation.

3. 2021-2023

   Identification of host factors of NTM diseases and bronchiectasis in the Asia-Pacific region

   Principal Investigator:

   Dr Ho Namkoong (Japan)

   Co-Investigators:

   Dr Rachel Thomson (Australia)
   Dr Byung Woo Jhun (Republic of Korea)
   Dr Naoki Hasegawa (Japan)
   Dr Kozo Morimoto (Japan)
   Dr Takanori Asakura (Japan)

   Project term

   1 January 2021 – 31 December 2023

   Project Summary

   Pulmonary nontuberculous mycobacteria (NTM) disease is a chronic progressive pulmonary infectious disease caused by low virulence pathogens. The number of NTM patients has been increasing globally, especially in the Asia-Pacific region. Our team has been elucidating these epidemiological findings and their clinical impact.
   Despite the dramatic global increase of NTM, issues such as ineffective antimicrobial agents, difficulty in the development of novel antimicrobial drugs, and risk of emergence of drug-resistant bacteria following long-term use of antimicrobial agents persist. Therefore, new strategies are warranted for better therapeutic options. Considering that NTM are ubiquitously present in the environment and have low virulence, these findings suggest a genetic predisposition to pulmonary NTM disease. However, there are few genetic studies on pulmonary NTM disease, and no genome-wide association study (GWAS) has been published for pulmonary NTM or Mycobacterium avium complex (MAC) diseases.
   The Japan and Republic of Korea teams conducted the first pulmonary MAC GWAS, including 2,064 patients and 3,063 controls, including Japanese, Korean and European populations. This study provides a basis for conducting further research with a larger sample size, and we plan to establish a global research network to identify susceptible genes for pulmonary NTM disease in the Asia-Pacific region using trans-ethnic meta-analysis of GWAS and exome sequencing of familial NTM cases. We will further perform functional validation of the identified regions to better understand the pathogenesis of pulmonary NTM disease.
   The project reports are published at pulmonaryinfection.com/ and pulmonaryinfection.wordpress.com/.