an enthusiastic undergraduate at the university of pennsylvania decides she wants to try a genetics project . she signs up for independent study with a fly lab . pretty soon , she and another student are ready to travel to brookhaven to irradiate the flies . the students and flies are picked up in philadelphia by a limo , taken to a small airport , and loaded onto a private plane . they get a great view of the coast as they travel north . at the other end , they are once again met by a limo . but it is no longer standard practice to transport your flies on private planes or coddle them with limo rides . the day - to - day practice of being a scientist has definitely changed in the past 40 years . aside from losing luxury travel and gaining computers , we have a lot more tools for our experiments . because students often take these tools for granted , it is particularly satisfying to teach about older alternatives and the transformative capacity of the new methods . one of my favorite questions to ask my undergrad class when i show them a picture of fluorescently labeled cells from 1970 is ,  how was this figure made ?  the students are stumped . if they get this , i 'll help them out :  the microscope had a film camera mounted on it . the person took a picture , then took the film to a darkroom and developed it to see if the image looked good . they almost never get the next part : scissors , glue onto paper , and rephotograph to make the final figure , then send in three prints of the figure for the reviewers . maybe it is because i really hated film and love being able to see my cells on the computer immediately , thanks to ccd cameras and imaging software . some other science tools that are particularly satisfying to teach are green fluorescent proteins ( gfp ) , rna interference , genome sequences , and pcr . the tools are very tangible evidence of the huge progress that has been made in the biological sciences . of course , having good tools is only useful if you have something compelling to do with them . during my research training , i was lucky enough to have four great mentors : carolyn machamer , jack rose , tom rapoport , and chris doe , who mixed guidance and freedom as needed . this means that at various times i had to think hard about what i really wanted to tackle . when i decided to join tom 's lab , he told me that i could pick anything i wanted to work on , with one condition : i had to aim to reconstitute it in vitro from purified components before i was done . i floundered thinking of something to work on , and ended up joining forces with another graduate student , pascal stein , on a project . we started off in the test tube , trying to reconstitute nuclear envelope assembly with frog egg extracts . it did not go well . after a year , pascal suggested we try to identify new nuclear envelope proteins using a strategy that stephen taylor had developed in frank mckeon 's lab . we moved out of the test tube and into whole cells to screen a gfp - cdna library . this worked out better , and we found a new protein ( rolls et al . , 1999 ) . pascal followed up on this project , and i was left once more to wonder : what question did i really want to ask ? in addition to working together on a project , pascal and i had started a journal club in the lab . as a result of reading and discussing papers in this group , i wanted to know how rough endoplasmic reticulum ( rer ) proteins are kept out of the smooth er ( ser ) , whether the er is continuous . i tried pilot studies in mammalian cultured cells , but they did not look promising . what i needed was a cell type in which the rer and ser were spatially separate , so i could distinguish them by light microscopy . muscle cells or neurons seemed most likely to meet this criterion , as they have large regions of ser . i considered two options for looking at these tissues : cultures of differentiated mammalian cells or whole caenorhabditis elegans . after some pilot studies , i decided c. elegans would be best , as i could look at both muscle cells and neurons using the same methods . the cells would be fully differentiated and functional in a see - through body , without any finicky culturing . i generated a new set of markers for c. elegans membranes , including rer , ser , golgi , and nuclear envelope . the only snags were that i did not figure out how domain formation in the er worked , only one way it did not work ( rolls et al . , 2002 ) , and also there was no way this project was going to end up with an in vitro reconstitution . two top lessons from this experience were : 1 ) choose the best system / tools to answer the question , and 2 ) cells can do very sophisticated things in vivo that they do not always do well in culture . if you are a new principal investigator starting your own lab , i know you have heard this . i hope that being somewhat focused but totally open to ideas from great colleagues and students works as well ! when i started my lab at penn state , there was one question that was begging to be answered first . as a postdoc , i had found that microtubules in drosophila sensory dendrites have microtubules with minus end  out polarity ( rolls et al . , 2007 ) , not the mixed polarity found in cultured mammalian neurons ( baas et al . , 1988 ) . i wanted to know whether this was limited to sensory neurons , or whether all drosophila neurons would share this microtubule organization . while michelle stone tackled this question ( stone et al . , one paper we really enjoyed showed that microtubules are dramatically rearranged near the cut site after injury of an aplysia axon in culture ( erez et al . , 2007 ) . michelle asked me whether we could use our drosophila tools to see whether something like that might happen to an injured neuron in vivo . she explained that when she was growing up her dad had a stroke , and it had changed him and her family forever . she wanted to do something to understand what went on in his brain during and after the stroke . we 'll see if we can come up with a way to injure the neurons in vivo . mark terasaki , whom i met when i was in grad school , had described to me a method to cut axons in vivo using a two - photon laser ( galbraith and terasaki , 2003 ) . but at some point i remembered that most c. elegans labs have lasers to ablate cells , and if you can kill a cell , you should be able to cut an axon ( c. elegans labs had also realized this [ wu et al . my next - door neighbor , wendy hanna - rose , is a worm person and a fabulous colleague and had a pulsed ultraviolet laser . the laser worked to cut axons , and she let us put it on our scope . almost immediately , michelle noticed not just local changes near the axon cut site , but an increase in the number of growing microtubules throughout the entire dendritic tree ( stone et al . , 2010 ) . this change was so striking that she ran into my office the first time she saw it and told me i had to come see right away . although we are now less focused on neuronal polarity , we are completely hooked on understanding neuronal responses to injury  something that would not have happened without several brains working together . i started in carolyn machamer 's lab at johns hopkins the summer before my freshman year at yale . in my second summer , she announced at a lab meeting ,  whoever wants to go to the ascb meeting this year needs to give me an abstract to look at by next week . i asked her whether this included me , since i was just a summer student . she froze and looked surprised as she thought about this , but replied after a while that the offer was open to anyone who could come up with a reasonable abstract . so i went , and i have gone back almost every year since then to learn about new tools and ideas and to hear great stories . following her example , we typically have 810 undergrads in the lab and constantly benefit from their enthusiasm and openness to new ideas . i have not yet brought any of them to the ascb meeting , but none has asked yet . a few last morals : if you do not ask , the answer is no ; be open to new people and ideas ; and , of course , enjoy your science !
tell a story , 
 my mother instructs her graduate students as they prepare their talks . 
 i will make use of her advice here , and will tell several short stories . 
 the themes revolve around the practice of science  what motivates us to go into science and how we choose questions once we get there . 
 i also touch on progress in scientific tools , teaching , good mentors , and good colleagues , all of which contribute to making a career in science constantly compelling .