Unfinished business and a follow up for Anil

Did anyone wonder if the mousse set and whether I hit the $60 mark? Almost and still don't know. I served the mousse in glasses, a forgiving receptacle for a slightly limp but nevertheless tasty mousse. In fact Nick, our technical guy, came over to talk to me at the end of the lunch- he appeared to have something urgent on his mind. Probably related to the conference I assumed, but no- he wanted the recipe for the mousse! As for the receipts I still have to dig them out- but I do remember you can get a 6 lb can of chickpeas for $5.99.

In an email, Anil expressed a hope that I would continue writing about courses I teach.  So this is for you Anil and it is something you are passionate about- reaching out. I have been going with a team of our undergraduates to local high schools to present DNA fingerprinting workshops.  It is a service learning class and we take our expertise and equipment to 10th grade biology classes so that the students can do DNA analysis to solve a crime. Imagine this. We transform the library into a lab and the librarian has to watch as the students pour liquids into plexi-glass gel boxes, don gloves and inject blue samples into slabs of jello-like stuff. As part of my rather goofy presentation I even pretend to steal one of the books. But as we left one school, the librarian claimed we worked a 'miracle' and that in her twenty years she had never seen the students so engaged and working so hard. 

The 'miracle' is of course the 5:1 student-mentor ratio and the undergrads themselves who are an order of magnitude cooler than me and most of the teachers! What we do is a drop in the ocean and there is no point in sugar coating it- the schools we visit are not places where learning is revered above all else. Neither was my English boarding school. I was a lack luster student- but the classroom was quiet and ordered and nothing prevented me from listening to the teacher except me. Today it all seems more chaotic. The movie shows what some of the Ohio State undergraduates thought about the workshops.

 

The student sessions

How lucky I feel to have such a rich intellectual life. How many people can say they spent Saturday morning listening to talented students across the globe talking together about issues at the frontier of science?

Hyderabad, sophisticated; Madras, highly informative; Columbus, provocative. Those are the words I would use to specifically characterize each talk.  In common, all were thoroughly researched, had excellent visuals, and were well presented. Hyderabad showed us that a talk with many presenters works beautifully- it flowed well and the changeovers added interest- well done! ( See what Lindsey said about this in the movie!) Vidya, it was good to see and hear you on the screen- and I wish you a happy Mother's day! Madras and Columbus you had some spirited exchanges (see the movie for the proof).

Alright so here is the bad part- it's over! Our wonderful course just ended. And we were just getting started discussing the proteomics-genomics divide again, when our system timed out and we didn't even have a  chance to say goodbye. We must rendezvous again and thoroughly talk the old rivalry out! Meanwhile here is a keepsake I made for you all- a three-minute movie.

The $60 lunch

I am on a quest of my own not for the $1,000 genome and the 'X prize', but to see if I can make lunch for about 20 people for $60- the amount we have in our budget. I think I just did. I will double check my receipts but it is too late (at night) to do that now. The mango mousse is in the fridge- the various dishes are in the slow cookers and I hope it will be alright. Everything is vegetarian- so the mousse is setting, I hope, with agar. Don't worry it is not from the lab, but a Thai food brand. My experience with making gels did come into play. I made what think must have been an equivalent of a 40% gel and then stirred it into the mango etc. I usually use gelatin, but we all know where that comes from. Except the guy in Whole Foods, who was quite surprised when I enlightened him. I am happy with the channa masala and the raita. But both the vegetable curry and yellow dahl dish are new to me. And scaling up is hard.

Venkat and I listened the OSU students practice their talk. I was very impressed. Venkat has seen the slides from the Hyderabad and Madras groups and was likewise impressed with the material. So the last session holds lots of promise.

The only disappointment I envisage is my mousse not setting.

Celebrity and concordance

Should we have anticipated anything other than concordance on either side of two oceans, as we picked over cases of ethical dilemmas in 'everyday' and 'big' science. Perhaps not but it was exciting to see our esteemed colleague, Dan Farrell, pump his fist when he heard students in Madras and Columbus independently reach the same conclusion about the set of moral values that were at stake in the cases.  Dan had a baptism by fire as he simultaneously debuted in video conferencing and PowerPoint, not bad for someone who claims to be a dinosaur. Dan also claims not to lecture- but he did a bit as he gave us a crash course in philosophy- were we realists or non-realists. Then we launched in and it was interesting- very. So yes even Dan's dynamic style can work in a video conference.  We are only sorry that technology did let us down as Hyderabad had internet issues and could not be 'present'. But we will all be able to watch the archive.

So what did we discuss at lunch.  Were any differences revealed that had a cultural basis? In the Hwang case, Dan had asked us to think only about one issue- was it OK for Hwang, the lab boss, to ask his female trainees to donate eggs for cloning experiments?  Everyone thought no, absolutely not. But in Madras the idea that this was also a breach  of etiquette came up.  We all agreed that this was an egregious use of power.  But in  Columbus we didn't think so much about it being an inappropriate male-female interaction. We then  launched into whether we were optimists or pessimists about the speed of change for inclusion and equality of women and minorities in science. Things rapidly devolved/evolved into whether we were all prisoners of our own biology. Destined to promote our own kind and maintain the historical male to female status quo. To be continued....

And now to celebrity. It came up twice in the day.  First, the idea of the celebrity effect was raised in relation to the fraud case involving  Schon and his famous boss Batlogg. Did Schon's work avoid an initial scrutiny because of his association with Batlogg? Do prominent scientists have an aura that protects them and makes them believable?

Second, later that day I heard a genomics talk from Robert Strausberg who claims to be the only one on earth to have worked for both people who have had their personal genomes sequenced!  These are of course Watson and Venter. And he, Strausberg, has had a dizzyingly successful career at the top level in public and private science. He is currently deputy director of the Venter Institute. So a private glimpse into the genomes of two celebrities, Venter and Watson.  Once alleles corresponding to 'risk takers' were revealed (the finding made quite splash) Venter wanted to know if he had the specific allele, some disappointment- no he didn't. If you compare the two genomes Watson is not as good at metabolizing drugs as Venter. But the bottom line is that for a healthy person, having their personal genome sequence really doesn't reveal that much, at least currently.  Strausberg emphasized the need for bioinformatics- to make sense of all this data. So for those of you who are starting your careers in science- take note!  Meanwhile the Sorcerer has set sail on a second expedition with Venter at the helm. Off to do some more metagenomics and combine his love of science and sailing- life's good!!!!

Fly feelings and feelings about flies

Last time I titled my blog 'getting to know you'. So do I know you? I was reminded today about how the 'lecture plan' has nothing to do with the 'what I would like to know plan'. What I wanted to skim, the group wanted to explore.  What I thought would provoke discussion passed quietly, and the ethical treatment of flies and how exactly dsRNAs get chopped up took center stage. Believe me when I say this is not a complaint but rather a plug for exchange and group discussion. Which reminds me- thank you for your interesting questions at the beginning of the session- Madras and Hyderabad.  

Nusslein-Volhard and Wieschaus conducted a Nobel-prize winning screen defining many genes that are required for the segmentation process in Drosophila.  The mutants they created had altered body plans and by looking at these 'broken' embryos the way a wild-type embryo is constructed emerged. A huge breakthrough for the field and a monumental forward genetic screen. I also showed Ed Lewis' amazing four-winged fly. I know we are all thinking about ethics,  in part because Dan Farrell's session on the ethical conduct of research is next week, but I didn't expect to be asked about the ethical considerations that come into play when so many fly embryos are used (well doomed) in an experiment.  Let me say straight away that I am the person who saves worms from the sidewalk on rainy days and I never met an animal I didn't like (except lions), but well flies.... I hope I answered the question sensitively because I do actually care about my flies quite a bit.  

This led to our lunch discussion and what kinds of animals feel pain- fish, frogs, cockroaches? Flies avoid odors associated with electric shocks but what does that aversion amount to? The vegetarians out number the meat eaters in the Columbus part of our class.  So then I felt bad about discussing the cow genome, because needless to say one of the driving forces behind that project is learn more about cows because they are a food product.  But at least Dominette, the DNA donor, looked fit and healthy! 

So let's stick to talking about dicing dsRNA and how you express it in one group of cells in the body and how long the double strand should be. All the things I thought would be less interesting than all the things I talked about instead!  

But I cannot resist showing you a picture of a fly with eyes all over its body. Repeating the classic experiment by my colleague Georg Halder when in 

Gehring's  lab - we make these every year in the undergraduate lab I teach! 

Getting to know you

Today's session was exciting. Venkat and I had learned a great deal from your feedback last time and incorporated questions and group work to make our lectures more interactive. Through this to and fro, we really are getting to know you! Thank you all for your great questions- Hyderabad, Columbus, and Madras.

At lunch following the session, we asked the OSU students what they expected to get from the course. One student remarked that she didn't really expect to learn new material, but that in fact much of it is new to her. I concur- a lot is new to me too, as I found out while preparing my lectures- the science we are covering will transform biology. On the other hand, another student was expecting to learn new material, but has been surprised by just how interesting the international component is. We were happy to learn that she had been chatting to student colleagues in India and then got to connect the names to the faces during the video introductions. How cool is that? (Sorry but in this case it seems to be the appropriate word.)

Next time I will be discussing functional genomics and as luck would have it a brand new fantastic paper was just published on genome wide RNAi in flies looking for Notch pathway genes. The Notch pathway is important in human disease and this is another case of using a model genetic organism for discovering the 'genes we share'.

It is a privilege to part of this joint enterprise and I thank you all for energizing me for the rest of the weekend!

Friday 17th - the view from my window

I have been thinking quite a bit about next generation sequencing versus microarrays. I am involved in a collaboration with a colleague at Harvard. The goal is to identify changes that occur when cells become 'immortal'. We planned to look for changes in the transcriptome using Agilent arrays. But why not also survey the genome for mutations? Next generation sequencing allows both in a single experiment because you get abundance (transcript level) and sequence information. So in the spirit of competition my last slide is to ask students and instructors at all the sites for their views on the relative power and merits of arrays and next generation sequencing for a given application.

Meanwhile here in Columbus it is sunny and beautiful. This is the view from my window. So you will see both kinds of 'football' represented in the video - the 100,000-seat stadium for watching the game with the oddly-shaped ball and some guys running around after a little round ball.

Thoughts after the first session

There are many levels on which to think about the first session. How was it technically? Good- we had one glitch with the graphics, but pointing the camera at the screen solved that. As someone who likes to make videos, I am going to use the remote next time and actively record Venkat as he speaks and switch to the audience for the questions. Let me compliment Madras- I think you had the most dynamic coverage! How was the content? There is no doubt the material is interesting. For my part, I know I rushed the next-generation sequencing and need to cover some of it again. I will do that- a recap that will fit well with the next topics anyway. Mike thanks for bringing the Scope and starting the STR analysis. I will be down to film you on Monday as you process the samples! Venkat, you have thrown down the gauntlet- I see this is a genomics versus proteomics competition. It is interesting how many 'omics' must be considered. Your point is well taken, as was an audience point that it is in fact the activity of factors (proteins, RNAs, and other molecules, comments on these anyone?) that really represent the phenotype of the cell. I look forward to the next installment!

After the session we adjourned to the room next door and ate pizza and Ruth's delicious homemade chocolate cake! We talked. Two main subjects: how did it go and what topics would be good for the student presentations? The students thought that more interaction during the session would be good. Together we came up with the idea of pairing students between the sites- so that we can learn more about each other. Probably most of this will go on behind the scenes. Venkat reminded us that this course is an experiment and that we could write it up as a paper for a science education journal. So I encourage you to do what I am doing now- write down your thoughts privately or publicly. Then we will have data.

Topics for student presentations. 1) The $1000 genome was the first idea and I have already blogged about it. 2) Functional genomics and/or genetic engineering. These topics are rife with Nobel prizes, science, technology and ethical issues. We struggled with a third equally interesting idea. Then Sathiya suggested: 3) Biology and law. A wonderful idea- how do findings in science get made into products? And if they do what happens next ? -an interesting mix of patents, generic drugs, money, egos and more!

Next generation sequencing- the movie

I met with Jeff and Tim who gave me a tour of the SOLiD system in the Department of Human Cancer Genetics. To tell the story I made this movie. Thanks, to you both. 

My interest in next and next-next generation sequencing is increasing the more I learn. Venkat and I discussed student projects and agreed that the quest for the $1000 genome (personal genomics) would be a very interesting topic. It could combine a Nobel prize (Sanger), technology (single molecule sequencing) and ethics (what are the implications?).

my first lecture

The history of genetics starts a long way back with the male- and blood-centric views of the ancient Greeks. Mendel the father of genetics changed everything with an experimental and quantitative approach that led to his two laws. He published his famous paper in 1866, but it lay dormant until its rediscovery in 1900. In 1983, Barbara McClintock received a Nobel prize for her work on transposons. Just as Mendel was ahead of his time- so was McClintock. She stopped publishing her results for a long period because of the skepticism of other scientists. The Nobel prize came some 40 years after her initial findings. The prize was a vindication for her and a landmark for women, as she was the first female scientist to win the "physiology" Nobel outright.

My first lecture is about some of this history and then goes on to genome projects and technology. I have been very struck by so-called next generation sequencing. It is amazing creative technology and quite simply mind blowing. It is all heading towards the $1000 genome. Imagine what that can mean for medicine and more. Perhaps Dr. Farrell who will be giving the ethics component of this class will have some comments.

Finalization of my lecture plan

I am now quite excited by the outline of my lectures and how they relate to the three timelines- landmarks in genetics, technology developments, and Nobel prizes. The connections are interesting of course. I talked to colleagues and asked them what I had missed. Depending on their own expertise they suggested certain things. For example, Boveri from a cell biologist and 'one gene one enzyme' from a Neurospora expert. My yeast colleague and I were talking and I will add the genome-wide yeast knockout strain library- that's genomics and reverse genetics!

Jeff, who runs the microarray core in the Cancer Center has agreed to star in a movie I will make about the 'Solid' sequencer he operates. This is one of the next generation seqencers. They use it to sequence microRNAs so it will connect to the content on several levels. The students I teach in another class toured his facilty and were very impressed with the million dollar machine!

The use of genomics in forensics will be another thing I discuss. Mike who runs the sequencing center in my building has a kit, which is the same one that the FBI use, so he can profile people for alleles at 13 loci. I have asked him if he will come to class to profile some of our students. I'm waiting to hear back from him.

Planning the course

Venkat and I visited the Learning Collaboration Studio, where the videoconferences will be held. It is a really nice room in many ways. There is of course all the technology, which was surprisingly easy to use (we think). Venkat said we were 'Luddites' but Meghan, who runs the facility, assured us that we weren't. In fact I like it very much and am excited at the prospect of this new way (for me) to teach and learn. We called into a test conference and talked to a guy in Philadelphia, who was preparing for a conference later that day. It was a chance to practice with the cameras, sound etc. The podium computer has 'Smart' technology, which means you can turn your mouse into a pen and write on the PowerPoint slides. We practised writing neatly and I drew some Drosophila (fruit flies).

I am finalizing my lectures. The overarching title is Genetics and Genomics in the Analysis of Biological Problems. Three timelines (landmarks in genetics, techniques, and Nobel prizes) will set the backbone. Certain topics in the timeline will be expanded and I will discuss three 'case studies' in detail.