Dr Hung-Ji Tsai

Supervisor Details

Contact Details

School of Biosciences, University of Birmingham

Scientific Background

Research Interests

Dr Hung-Ji Tsai is interested in how aneuploidy, an unbalanced genomic state with gain or loss of chromosomes, enables rapid adaptation to diverse environment. His research focus is to understand the distinct cellular processes driven by aneuploidy (and other large-scale genome instability) during the acquisition of antifungal drug resistance.

Our research group is broadly interested in how cells survive stress conditions. A major focus is to investigate the molecular mechanisms in response to stress in cells with ongoing large-scale genome instability, mainly in aneuploid cells. While aneuploidy is frequently observed in eukaryotic genome and generates genetic diversity, the physiological impact of aneuploidy contributing to cellular adaptation under stress remains poorly known. We aim to study:

How do aneuploid cells respond to stress?
How do aneuploid fungi interact with the host during the evolution of drugs?

Our group employs molecular tools, experimental evolution, genomics and cell biological techniques to address fundamental questions in fungal species, including Saccharomyces cerevisiae and Candida albicans.

Supervision Style

In three words or phrases: Detail-oriented, supportive, goal-driven.

Provision of Training

At the beginning of your training, I will work alongside the student to support the development of experimental skills and to help the student establish a solid foundation of scientific methods and experimental discipline. By the end of the PhD, I expect the student could have the ability to initiate new ideas/projects with rational, feasible experimental plans and meanwhile possess the ability to write research manuscripts and proposals, as an independent scientist.

Progression Monitoring and Management

I expect the student to take full ownership of the project progression, but I will be available for troubleshooting to facilitate the student’s project. A weekly personal meeting will also be set up to discuss plans of action and related lab matters.

Communication

I reply emails from my team at all hours (not expect the student to do the same), in response to any timely needs in the lab or data analyses, and a lab SLACK group is set up for the lab members to facilitate the communication. I am also happy to discuss any issues regarding career development in personal meetings and will proactively initiate the conversations at every milestone during the training.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per fortnight

In year 3 of PhD study

At least once per fortnight

These meetings will be a mixture of face to face, via video chat or telephone, and I am usually contactable for an instant response on every working day.

Working Pattern

Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

Project Details

Dr Tsai is supervisor on the below project:

Investigating the effects of microenvironment cues on fungal adaptation

Secondary Supervisor(s): Dr Megan McDonald

University of Registration: University of Birmingham

BBSRC Research Themes:

Sustainable Agriculture and Food (Animal Health & Welfare, Microbial Food Safety, Plant and Crop Science)
Understanding the Rules of Life (Immunology, Microbiology, Systems Biology)

No longer accepting applications

Project Outline

Background

The rapid emergence of fungal diseases is a global threat to animal, plant and our ecosystem, while fungal infections affect billions of people, including >1.5 million global deaths each year. Within a fifteen-year period (1995-2010), fungi have caused species extinction of 39 animal and four plant species [1], and there are only three classes of antifungal drugs available in the clinic in the past four decades. Inevitably, multidrug resistance has become an urgent problem for the agricultural industries and human medicine. Additionally, with climate change, extreme weathers also facilitate the interactions between fungal pathogens and their host (and/or environment), and many environmental fungi now can overcome growth temperature barriers (12–30°C) to affect human [2]. The development of stress (thermo-) tolerance phenotypes likely results from the high genome plasticity in fungal genome, while aneuploidy, an unbalanced genomic state with gain or loss of chromosomes, is prevalent in wild and clinical fungal isolates. Whether and how these genome abnormalities alter the host-fungal-microenvironment interactions to enable adaptive evolution in fungi remain elusive. This project aims to investigate the evolution of host-fungal interactions under environmental stress and to identify novel host and fungal factors contributing to the pathogenicity.

Objectives and Methods

We will use multiple fungal pathogens (mainly Candida species) and animal, cell line infection models to investigate the phenotypic cues governing stress tolerance at the host-pathogen interfaces.

Objective 1: Characterize stress-induced fungal secretory profile

While aneuploid fungi share a unique biophysical signature, hypo-osmotic stress state [3], the increased turgor pressure can lead to a unique secretory profile, including proteins, nucleic acids and metabolites. We aim to systematically identify and characterize their function and contributions to stress tolerance phenotypes and species interactions, using multi-omics approaches. The research outcome of this objective will reveal the mechanistic insights into how fungal pathogens tolerate antiproliferative stress and thrive from the host microenvironment.

Objective 2: Investigate the fungal genomic plasticity at the host-fungal interface

As fungi possess a high level of genome plasticity, we will identify the types of genomic alterations (mutations/CNV/ploidy variations) when fungal pathogens encounter the host and environmental stress in a temporal manner. Importantly, the mutual relationship between each type of genomic abnormalities will be investigated. For example, whether ploidy variations “buffer” or promote DNA damage responses? Both genomics and cell biological methods will be used to reveal the mutational evolution in the adaptive process.

Together, this project will leverage both genomics, proteomics, biochemistry and cell biological approaches to understand the molecular evolution of fungal diseases from the interactions of hosts, fungal pathogens and their microenvironment.

References

Fisher, M., Henk, D., Briggs, C. et al. Emerging fungal threats to animal, plant and ecosystem health. Nature 484, 186–194 (2012). https://doi.org/10.1038/nature10947
Case NT, Berman J. et al. The future of fungi: threats and opportunities. G3 (Bethesda). 2022 Nov 4;12(11) https://doi.org/10.1093/g3journal/jkac224
Tsai, HJ., Nelliat, A.R., Choudhury, M.I. et al. Hypo-osmotic-like stress underlies general cellular defects of aneuploidy. Nature 570, 117–121 (2019). https://doi.org/10.1038/s41586-019-1187-2

Techniques

Molecular technologies: both basic and high-throughput lab techniques, including genome-wide screening and strain manipulations in automation systems.
Biochemistry: protein purifications, western blotting and immunoprecipitation assays.
Cell biological methods: advanced quantitative microscopy, phagocytosis assays and related host-pathogen interactions assays.
Basic animal model of infections.
Genomics: genome-sequencing, barcode-sequencing.
Proteomics: LC/MS-based quantitative proteomics.

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