Questions and AnswersProf. Dr. Siamon Gordon

How or why did you become involved in infection research, what fascinates you about this subject?
As a medical student, from pathology course at the University of Cape Town, I was influenced by a lecturer Golda Selzer, a rare researcher in polio vaccine, who subsequently arranged for me to start my research career in the Porter lab (Wright-Fleming Institute, St Mary’s, London) with Sidney Cohen, on antibody structure, and at Rockefeller University. After a post-doc year with Alexander G Bearn, a human geneticist, with whom I worked on haptoglobin, I undertook a PhD in macrophage cell biology with Zanvil Cohn. The rest is (personal) history.

What are you working on at the moment?
As ever, diverse aspects of macrophage immunobiology, mainly in mouse models relevant to human disease. Focus is on non opsonic receptors (scavenger SR-A, Marco); Lectins (dectin-1) and regulatory surface molecules (EGF-TM7, CD200, Dap-12), implicated in predictable interactions with endocytic, phagocytic, infectious (Neisseria, Dengue, Candida) and non infectious host-derived ligands (apolipoproteins) and some less obvious functions (especially mannose receptor role in antigen targeting, alternative macrophage activation, tumour associated macrophages). A particular fancy is the mechanism and possible function of macrophage cell fusion in granuloma and osteoclast formation (an old love since student project 40 years ago).

What were the turning points in science, in career, in life that influenced your decisions?
In Cohn laboratory (also with James Hirsch and René Dubos (a Pasteur scientific descendant) I became hooked on macrophages and host-pathogen interactions (with a touch of social and historical interest in tuberculosis). I was also influenced by Henry Harris’ dramatic experiments in Oxford on Sendai virus – induced cell fusion as a research tool, which provided a thesis topic and eventually took me to a position at the Dunn School of Pathology, where I’ve been since 1976 until my formal retirement in 2008.

What was a single most important moment of your career?
My attempts to study heterokaryons and hybrids (somatic cell genetics, cell differentiation), using macrophages as tools ran into the technical limitations of single cell analysis – so I made a conscious decision, sometime around 1970 to study primary macrophages for their own sake. This led to the study of lysozyme as a secretion product, a neglected function of this professional phagocyte.

What was your most important scientific discovery?
Following on secretion of lysozyme and plasminogen activator, macrophage activation (including alternative pathway induced by Th2 cytokine). Application of hybridoma technology (a natural evolution given my background) to macrophage differentiation antigens. This led to F4/80 and definition of the mononuclear phagocyte system throughout the body; their role in development and disease, and production of new functional monoclonals to study adhesion (CR3, SR-A), new receptors (Sialoadhesin, Dectin-1, mannose receptor) and modulators of fusion. Of course I also missed a few even more important molecules – TNF and TLR!

What drives you and carries you on? What do you love about your work?
Curiosity, ­imagining the way Nature works. Talking about macrophages.

What influenced and impressed you and your life and therefore science?
The feeling of past discoveries and institutions with strong experimental traditions (Rockefeller, Dunn School), provided a sense of freedom, daring and confidence. The drive to discover new things that matter.

Idols?
While I have a deep sense of gratitude to my above mentors, I love to go against the stream, appreciate my teachers, but not to idolise.

What would you recommend to someone starting out in science? What would be your advice for young scientists?
Grow slowly, don’t rush or follow bandwagons, find topics of broad biological interest, especially at interface between narrowly defined disciplines.

What would have been your alternative plan (plan B) if science/your job had not worked out?
If I had grown up in a less provincial society (Jewish South Africa), I would not have become a doctor and subsequent scientist (which I have never regretted), but studied and researched in the humanities (social science, history).

What are your dreams for the future?
To integrate knowledge of my favourite cell in a wider context.

What do you think is important and should be worked on in the future?
The trophic functions of macrophages (haemopoiesis, brain) are neglected, nor is their differentiation in disease tissue microenvironments understood at all.

What do you do when you are not working?
Mulling over the macrophage, while reading broadly and listening to 18-20^th century music, especially Schubert.

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