 I'm Joe, the Communication Officer for FEMS and I'm joined today by Professor Graham Walker from MIT and we're here in the Mediterranean Institute for Life Sciences at the FEMS summer school for postdocs and this morning you gave a lecture to the postdocs so do you mind just give me a brief overview of what you're discussing? Well since this conference is on bacterial stress and I and also my co-director Murrow Radman did a lot of the early work and what's now known as the SOS response that we call I so rather I tried to sort of tell students who didn't know everything about it something about the system but not by giving a model and telling them where it was I tried to do it in a way that was more historical as I experienced that who had done what in the early beginnings of the field and then once I got into it what I saw as key experiment that would move it forward and then a new puzzle would arise and you'd have to come at it with a different angle and you get another insight and then another puzzle and or an unexpected direction yeah so trying to hope that I could convey something about how science was actually done and how it felt at the time because I don't know there's some wonderful young scientists here and they're going to be doing things we can't predict but I'm sure they will experience all of the same things that everybody else does as they go along so I was trying to pass on some of my experience and life. Well I think it went down well so my next questions are ones I just try and ask as many microphones as possible and the first one is what's your favorite microbe and why? Well I don't mean it's the ones you work on I guess I've worked on I started with Salmonella in Bruce Ames lab that was where I went as an organic chemist basically nucleic acid or organic chemist went to learn microbiology a little bit with Salmonella initially but for the problems I was addressing with the SOS the interesting mutants were in E. coli so that's what I've worked on all my career but then while I was a postdoc in the mid 70s and I was at Berkeley recombinant DNA was developed across the bay in her boyer's lab in Stan Cohen's lab and at the same moment transposons became a thing and I could see that even organic chemists could use those tools to take any bacterium and make a system that was very much like E. coli in terms of what you could do genetically so at that point I thought well I should pick something that does something interesting and I started to work on Rhizobium because it did the symbiosis with the plant but it was for me it was it wasn't it wasn't intrinsically trying to solve some problem in nodulation I just saw that you could ask the same level of detailed genetic questions in some other organism and I've worked with Rhizobium so all kinds of bacteria. Well I love that most people are like I don't have one don't make me pick just one it's too hard. Yeah I mean it's the problem I'm interested in and then sometimes they're the same solution of the bacteria sometimes different solutions and I talk I think I was talking to some students at lunch about when I was working on I haven't talked about it here particularly but on the Rhizobium symbiosis and I found genes that were necessary for the bacterium to live inside of a eukaryotic membrane compartment inside of the plant cells inside the nodule which is where it fixes nitrogen and it's an alpha protea bacterium and it's very closely related to brucella bordus and other species that live inside of a membrane compartment inside of a eukaryotic animal or mammalian cell and I thought when we found a gene that was critically required in rhizobium maybe it was needed by brucella which might have seemed like a crazy thing but in turned out a gene needed for chronic infection by rhizobium was needed for chronic affection in brucella so there one sort of an experiment in one organism triggered an interest in another that I never worked on and I had to get a collaborator but it worked out sounds cool like a fun yeah okay um well so my second question then is you can't do science without people so what's your microbiota or who is your microbiological hero and why and they could be someone you know or don't know but anyone particular who struck you as someone you'd like to give an accolade to uh I there were a number of influences um my first powerful one was my post-doc manager Bruce Ames I was a grad student in Illinois I heard him give a seminar and I was at that point getting conversant when you click acid chemistry in a bit with the click acid biochemistry but I could see I thought when I heard him talk I said he knows how to think like a cell and I was drawn to him not only because of the science he'd done but I wanted to sort of learn if I could somehow grasp how to think physiologically and not just learn genetics and then when I came to MIT I was very powerful there were a number of excellent microbiologists from Boris MagaSanic who worked on nitrogen metabolism uh Salvador Luria my colleague Nobel Prize winner founder of our cancer center and Mori Fox who's very very thoughtful about DNA repair and David Botstein who was a huge influence on me he was a bundle of enthusiasm about all things genetics so I think those in particular and then other along the way other that I could keep going for probably an hour but the people influenced me so there's never one single person because I sort of drifted into it and yeah from a different kind of chemical training and then I I still to this day have people that I get excited by and I learn things from okay well I'm glad there's many at least oh there's many and um yeah so my final question then is uh what one piece of microbiological knowledge should the whole world know about if you could somehow make everyone understand one fact or one piece of descriptive knowledge about microbiology what would you what would you pick well I guess I've done a lot of teaching and a lot of interacting with lay folks and I I think it's probably better known now than it was a few years ago but for many people the only thing they knew was that bacteria made you sick and you took an antibiotic and killed them and they went away they had no sense of how many bacteria we have in our intestine what an astonishing number that were covered with bacteria that they're absolutely everywhere the microbiome you know is an influence on all kinds of factors of health and I think that part of it is now better understood now but I think there are many people you know the world I live in is probably heavily still populated by people who have some amount of education I think there are a lot of people don't understand there's this unseed world out there and the other thing for me that was important I think was that that's so much of evolution happened at the level of bacteria there first life 3.8 billion years ago and eukaryotes didn't come around for a long time so it's not surprising that amino acid biosynthesis and principles of DNA replication and translation and ribosomes and everything were all worked out in in bacteria and I found it fascinating that you know especially in the earlier parts of my career things like DNA repair and stuff like that that the counterparts were either there directly as homologs in mammalian eukaryotic cells or they was convergent evolution and come to the same solution but using a different protein or something that the power of the bacterium is a model for other things and both Merrow and I did work with mismatch repair I sort of got mutants and mutas and mutal which are key components of the post-replicative mismatch repair system and improves fidelity after DNA replication and when I clone them I tried to publish it back to back I contacted a group who I thought had the same gene it was called hexa but from streptococcinemoniai we could see there were homologs and I tried to publish it I think in PNAS and the reviewers said this was of absolutely no interest there should go on especially journals we published it in journal bacteriology the sequence came out and my phone started to ring by people who were calling me to tell me that mammalian cells had a mutas homolog ironically one of them was located I think on the other side right beside dihydrofolate reductase and in the old days we didn't know so much about DNA so they'd sequenced in the wrong direction initially and they had an an orph of unknown function and and since then people went on within about a year or less than two years people had understood that hereditary non-polyposis colon cancer which is now known as Lynch syndrome and the familial susceptibility to colon probably ovarian cancer comes about in some cases by defects in the mismatch repair system and you accumulate mutations at a much higher rate and that was a case where the work in bacteria directly informed the our understanding of humans so that was the other sort of aspect microbes as microbes and their role in that but also microbes as model systems to understand what happened in evolution and gain insights into humans too cool well thanks a lot for spending some time talking to me and I hope the rest of the summer school goes well and thank you I think it's terrifically exciting idea I'm spending time with the postdocs and they're they're just wonderful and well let's hope to get another one yeah yeah thanks a lot thank you