18 Mar 2019

HKU-Pasteur is now on Instagram!

HKU-Pasteur launched its Instagram account this week: @hkupasteur!

Stay tunned on Instagram to follow the latest news of the Pole, our publications and events, HKU-Pasteur courses, and of course, the life of the Lab. 

Follow us, share the news, and see you soon!

09 Jan 2019

Congratulations to Fionn Ma!

Another graduation at HKU-Pasteur! Supervised by Roberto Bruzzone, Fionn Ma got her MPhil with her thesis titled “Investigation on the Functional Roles of Interaction between Human Karyopherin Isoforms and Nucleoprotein of Influenza B Virus“.

She will now work as a Research Assistant in Sophie Valkenburg’s team to continue her journey in HKU-Pasteur Research Pole.

Summary of her thesis:

Influenza B viruses are capable of causing disease with severity similar to that of influenza A. Nonetheless, unlike influenza A viruses that naturally exits in waterfowls, influenza B does not have an established animal reservoir and is largely restricted to humans. Factors determining the host specificity of influenza B virus have not been well studied. To establish interspecies transmission, a virus must be able to propagate efficiently in host cells of both species. The nuclear translocation of viral proteins of the ribonucleoprotein complex (vRNP) is a crucial step during virus replication, which relies on a group of cellular protein called karyopherin subunit α (KPNAs). These KPNA isoforms recognize nuclear localization sequences (NLS) on vRNP components and other cargo proteins and facilitate their transportation across nuclear pore complexes (NPC).

In this study, we showed that the nucleoprotein (NP) of influenza B virus interacted with human KPNA 1, 2, 3, 4, and 6. KPNA silenced human cells were employed to determine the roles of each KPNA on viral polymerase activity, transcription efficiency and virus replication. We showed that absence of KPNA2 decreased the polymerase activity of influenza B for 60%. However, KPNA2 silencing did not affect viral transcription and replication in our infection model. From our transcriptomic analysis, distinctive cellular responses were triggered between the cells infected by influenza A and B viruses suggesting that the two viruses may adapt to different strategies upon infection.

Given that studies on influenza B viruses are relatively limited compared to those on influenza A, our study gained a better understanding on the interplay between the host factors and NP of influenza B virus.

We wish you all the best Fionn! 

07 Jan 2019

Tremendous success for the 10th Immunology Course Anniversary Symposium!

Welcome back! For the 10th Anniversary of its Immunology Course, HKU-Pasteur hosted a world class symposium with the course alumni and special guests. 

In front of a packed seminar room, the day started with welcome addresses by Suet-Yi LeungAssociate Dean (Research) of the LKS Faculty of Medicine of the University of Hong Kong, Leo Kung, Chairman of the Pasteur Foundation Asia and a video message by Alexandre Giorgini, Consul General of France in Hong Kong and Macau. The symposium was a great success for everyone, a prestigious event in a warm and friendly atmosphere. All day long, alumni from all over the world shared their experience and projects, took part in a poster presentation session and enjoyed being back together after many years. 

It was also the occasion for the 2018 students to meet their predecessors and discuss career paths and experiences, as this day concluded the 10th Immunology Course, starting a new batch of alumni that will strengthen this amazing network. 

This hectic day ended in a joyful and festive ambiance over dinner, celebrating immunology, knowledge and the Pasteurian values. A great way to start the festive season! 

HKU-Pasteur wishes to thank all participants, students, alumni and guests, with special thanks to Leo Kung and Suet-Yi Leung, for their speech during the opening ceremony, to Alexandre Giorgini, who took the time to record a welcoming video, to Kanta SubbaraoWHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia, and Jean-Marc Cavaillon, Department of Infection & Epidemiology, Institut Pasteur, Paris, France, for their captivating presentations. 

We hope to see you next time for another exciting event! 

In the meantime, don’t forget to subscribe to our Newsletter, our Facebook page, group and LinkedIn Alumni group! 

Roberto Bruzzone, Co-Director of the HKU-Pasteur Research Pole and Immunology Course Co-Director, opening the symposium.

Leo Kung, Chairman of the Pasteur Foundation Asia, and Malik Peiris, Co-Director of the HKU-Pasteur Research Pole.

Suet-Yi Leung, Associate Dean (Research) of the LKS Faculty of Medicine of the University of Hong Kong.

Video message by Alexandre Giorgini, Consul General of France in Hong Kong and Macau.

Jean-Marc Cavaillon, Institut Pasteur, France.

Kanta Subbarao, the Peter Doherty Institute for Infection and Immunity, Australia.

Leo Kung, James Di Santo, Institut Pasteur Paris (France) and Immunology Course Co-Director, Keiji Fukuda, Director of the School of Public Health of the University of Hong Kong.

Sophie Valkenburg, HKU-Pasteur Research Pole, Immunology Course Co-Director.

03 Dec 2018

Congratulations to Akhee Sabiha Jahan!

Great news at HKU-Pasteur! Akhee Sabiha Jahan successfully defended her thesis “Role of deubiquitylases in Influenza A virus infection and immunity“. 
Supervised by Sumana Sanyal and Roberto Bruzzone, Akhee has been part of the HKU-Pasteur team since 2014. She was selected earlier this year to give a talk during the Keystone symposium “Framing the Response to Emerging Virus Infections” on the subject of upregulation of deubiquitylases upon infection and its role in antiviral immunity, and the role of OTUB1 in the context of Influenza A virus function and innate immunity. 
Congratulations Doctor! 
“Ubiquitylation is a cellular post-translational modification (PTM), routinely targeted by pathogens to deregulate and hijack host intracellular pathways. During Influenza A virus (IAV) infection, the host ubiquitylation machinery is significantly altered and exploited for RIG-I mediated viral sensing and immune response. To comprehensively characterize the ubiquitylation machinery hijacked by IAV in mammalian cells, we designed and employed a chemoenzymatic strategy to identify specific deubiquitylases (DUBs) that are induced upon IAV infections. Using a C-terminal vinyl methyl ester modified HA-tagged ubiquitin (HA-Ub-vme) combined with large-scale immunoprecipitation and mass spectrometry we identified DUBs that are upregulated in IAV infected cells. 
Among others, OTUB1 was identified as a deubiquitylase that is upregulated upon IAV infection. Interferon β treatment alone could also induce OTUB1 expression in A549 cells, suggesting it is an IFN-I induced host factor. To functionally characterize OTUB1 in IAV infection, CRISPR/Cas9 genome editing was utilized to generate OTUB1-deleted A549 cells. OTUB1-deficient (OTUB1-/- ) cells produced significantly less viral progeny, which were rescued by introduction of OTUB1 in OTUB1-/- cells. Further investigation showed severely defective polymerase activity in OTUB1-/- cells compared to WT. Influenza A viral protein PB2 which is essential for viral polymerase activity interacted directly with OTUB1 as measured by co-immunoprecipitation and co-localization score. Lack of OTUB1 was shown to be associated with a higher K-48 linked polyubiquitylation of PB2, suggesting a vital role of OTUB1 in regulating polymerase activity through deubiquitylation of PB2.
Additionally,  OTUB1-/- cells were defective in production of both IFN-α as well as pro-inflammatory cytokines compared to the WT when subjected to IAV infection. Further investigation of OTUB1-/- cells upon infection showed a significant redution in IRF and NFB activation, upstream of IFN and cytokines respectively. Through the use of proximity-based labeling, components of the RIG-I signaling pathway were found to be highly enriched in the OTUB1 interactome. Furthermore, OTUB1 was shown to directly interact with IAV viral protein NS1 known for its RIG-I antagonism and was shown to be degraded without proteasome inhibitor treatment upn IAV infection. Immunoprecipitated NS1 samples were shown to be enriched in K-48 and K-63 linked polyubiquitylation and formed complexes with TRAF3 and RIG-I, which have been previously reported as NS1 interactors. In OTUB1-/- cells, neither the ubiquitylated material, nor the RIG-I complex was detectable upon NS1 pull-down. The NS1-RIG-I interaction is known to be integral in the function of NS1 to limit IRF and NFB activation, eventually leading to dampened antiviral response. We find OTUB1 to be an essential determinant in the formation of NS1-RIG-I complex and mediation of the downstream antiviral responses. 
Apart from innate immune responses associated with IAV, ubiquitylation also plays a significant role in the adaptive immune responses, such as T cell receptor (TCR) signaling. We identified Ubiquitin-specific peptidase (Usp) 12 as a positive regulator highly enriched T lymphocytes and a crucial component of TCR expression at the cell surface.  These findings provided novel insights in fine-tuning host signaling cascades both in IAV infection and immunity, identifying new avenues for the development of potential therapeutic targets.”
If you want to know more about Akhee Sabiha Jahan's work, you can read this paper published in PNAS: Usp12 stabilizes the T-cell receptor complex at the cell surface during signaling
Roberto Bruzzone, Akhee Sabiha Jahan and Sumana Sanyal.
Sumana Sanyal's team.

14 Sep 2018

The Consul General of France in Hong Kong and Macau Alexandre Giorgini visits HKU-Pasteur

Two weeks after his introduction as the new Consul General of France in Hong Kong and Macau, Alexandre Giorgini made a point to visit HKU-Pasteur Research Pole to emphasis the support of France to the laboratory, and moreover, to research in general.

After visiting the facility, he took the time to meet the team at HKU-Pasteur and to discuss with our team leaders, Chris Mok, Sophie Valkenburg and Suki Lee, to better understand the missions and the challenges in HKU-Pasteur.

The Consul General reaffirmed that the joint laboratory, established by Institut Pasteur and HKU, is a great model of the collaborative success between France and Hong Kong, and an example of cooperation for future projects.

14 Sep 2018

[Testimonial] Marie Laclide, summer intern at HKU-Pasteur

Can you introduce yourself and tell us about your studies and why you choose HKU-Pasteur for your internship?

I am a French fourth-year medical student in Bordeaux, France. I did this two-months summer internship as a part of the research program my university proposes. As my dream speciality is infectious diseases, it is very naturally that I thought about the Institut Pasteur International Network. Also, Hong Kong was the ideal match for me as I used to live in China before and initially planned to practice Chinese. 

Can you tell us about your experience here for the last two months?

At first, I was trained by João Pombo, who is a Mphil student here in HKU-Pasteur. He is very passionate about his work and has the talent of passing along his passion. I was very lucky to have him as a tutor and he was the most supportive and available, always answering the thousands of questions I had with kind patience.

As soon as I got used to the lab, I started working on my internship project, which was a small sliver of a much larger project. The fact that I had to cope with all aspects of scientific projects, from the design and planning of the experiments to their performance really made it a thrilling experience.

What are your plans for the future?

Before this internship, I had never really considered working in a lab but I was surprised to find out a stimulating and creative atmosphere in the lab, I loved the comradery, and how people have a profession where they can explore their curiosity and people give them freedom to do whatever they want.

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