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Interviews with ISICR Milstein Award winners

Takashi Fujita

& Michael Gale, Jr. PhD

ISICR: Congratulations on receiving the Milstein Award this year! Where were you when you first found out that you have been selected to receive the prestigious Award?

T Fugita: I was in my office at Kyoto University one Morning. I received a call from ISICR president, professor Otto Haller.

M Gale: I was in my office meeting with one of my students, actually discussing mechanisms of RIG-I signaling. Otto Haller called me with the nice message that I had been selected to share this award with my friend, Takashi Fujita. Takashi and I enjoy a productive collaboration on research involving RIG-I and IPS-1. I am very happy to share this award with Takashi.

ISICR: What do you feel are your most important contribution to the field of cytokine research?

T Fujita: Many attempts were made in the last 50 years to identify molecule(s) that initiate type I interferon activation signal. It was known that replicating viral RNA triggers the signal, but its sensor was not identified. RIG-I helicase is the long sought sensor for replicating virus.

M Gale: My own research interests are focused on understanding how viruses trigger and control host defense and IFN actions, and on how regulation of host defense and IFN processes can define the outcome of infection. A major area of our work has been centered on hepatitis C virus, which is a global public health problem. An important contribution of my group's research is having defined a major intracellular host defense pathway that is responsive to and regulated by HCV. Our work suggests that the RIG-I/IPS-1/IRF pathway is targeted and regulated by HCV during infection, which in part allows the virus to persist in millions of infected people. We defined a new class of antiviral drugs, the HCV protease inhibitors, as host response modulators because they release the HCV blockade to the RIG-I pathway by interfering with a viral enzyme that otherwise cleaves and disables IPS-1. This gives us hope that these compounds will function to restore innate antiviral defenses in clinical practice.

ISICR: Why so many different names - MAVS, IPS-1, VISA and Cardif – for one protein? Do you have a favorite?

T Fujita: Four groups independently identified the downstream adaptor of RIG-I. Although the molecule is registered in the database, it did not have a name. The four groups gave different names. RIG-I family is troublesome in the other way. RIG-I (retinoic acid inducible gene I), MDA5 (melanoma differentiation associated gene 5) and LGP2 (laboratory of genetics and physiology 2) are recently implicated for the regulation of antiviral innate immunity. These had names before their functions were discovered. I would propose new names such as, HElicases for Cytoplasmic Signaling (HECS-1, -2 and -3).

M Gale: All the names are good and are descriptive acronyms. When we identified this molecule we were going to call it yet another name but have since used IPS-1. I agree with Tak: A nomenclature committee should consider this issue.

ISICR: What ignited the fire in you to become a scientist? Who was your mentor or role model in your scientific career?

T Fujita: I was fascinated by chemistry at high school. Dr. Seiya Kohno, my thesis advisor, gave me introduction to interferon research as well as being scientist. I learned the bases of molecular biology from professor Tadatsugu Taniguchi.

M Gale: I always liked to know the mechanics of how things work. This has not changed. I have a long background in the lab starting from student helper to tech to grad student, post-doc and PI. I was mentored by several outstanding people over this time line. Looking back now, I think the answer to the second part of your question comes from two traditional areas of training, grad school and post-doc. As far as a pure scientist, my mentor in graduate school, Dr. Marilyn Parsons, has been instrumental in my understanding of the scientific process and was a major force in my training in molecular biology and cell signaling. She is an outstanding scientist that brought me into a realm of pure science, so this was a powerful mentored experience. As a student I was highly influenced by the work of Dr. T. Taniguchi and his group's identification of new transcription factors called interferon regulatory factors (IRF) 1 and 2 (Takashi Fujita was involved in this work!). This made an easy decision for me to conduct post-doctoral research in the IFN arena. My interests in IFN and protein kinase signaling came together, as I joined the lab of Dr. M. Katze to study PKR and IFN for my post-doc years. Dr. Katze mentored me in new areas of virology/IFN biology, and really focused on improving my skills in writing, verbal presentation, and grant writing.

ISICR: What do you think are the components of a successful lab?

T Fujita: Free ideas, Love to explore facts, Patience.

M Gale: Good interactions, having bright and talented people next to you, and collaborating with other talented scientists.

ISICR: If you weren't a scientist, what would you be?

T Fujita: School Teacher

M Gale: Maybe a laid back fisherman or an engineer/chemist working in the area of alternative energy sources.

ISICR: What keeps you up at night?

T Fujita: Various things: Research, Next morning’s cooking eggs, How to fix my bicycle, A new joke…

M Gale: My teenage daughter is dating...

ISICR: If you could change one thing in your career, what would it be?

T Fujita: Do undergraduate or graduate study in foreign school.

M Gale: Actually I would not change a thing.

ISICR: This year's ISICR meeting will take place in the beautiful city of Vienna, Austria. The name of the city alone evokes thoughts of great music. What music is in your CD player these days?

T Fujita: Rachmaninov.

M Gale: Right now I have a CD in the player from a group called Antigone Rising. I am a piano player since age 8, trained in classical piano, so Mozart is my all time favorite. Vienna will be special.