Every cell in your body contains the same DNA, with genes coding for many thousands of proteins. Yet a muscle cell makes a very different set of proteins from say, a bone cell, enabling it to perform its muscle-specific job. Lorenzo Puri, M.D., Ph.D. and his lab members study what makes stem cells (precursor cells) choose to produce the proteins that turn them into muscle cells. In doing so, they hope their research will one day help improve strategies for muscle regeneration in patients with muscle wasting diseases, such as muscular dystrophy. While a cure for muscular dystrophy is not yet in sight, the ability to stimulate muscle stem cells to generate mature muscle cells could make a big difference in the lives of patients. By repairing muscles damaged by the disease, muscle regeneration therapy would extend the lives of patients and allow them to function effectively in a whole range of activities that are currently unthinkable for victims of the disease.
Charles Percy Snow (1905-1980), English author, physicist, and diplomat (Image by ©Bettmann/CORBIS)
A member of Sanford-Burnham’s faculty reflects on history, philosophy, society, and what it takes to get science done.
In 1959 the British physicist C.P. Snow delivered a lecture, and subsequently published a monograph, entitled “The Two Cultures,” describing what he saw as a growing divide between science and the humanities. Snow was afraid that science, spurred by the success of Sputnik, the resulting space race, the growth of nuclear technologies, and the very beginnings of the revolution in molecular genetics, would produce a culture that was impenetrable to non-scientists and in which scientists would be so specialized that they lacked the ability to connect with the rest of society. The publication was assigned reading for many university students at that time, and triggered many discussions about the balance between science and other aspects of society. Partly as a result of such discussions, a number of institutions of higher education were motivated to realign their curricula to make sure that science majors still learned about the roots of western civilization, including literature, art, and philosophy (with notable lack of foresight, nobody was thinking much about Asia in those days!). Oddly, in many cases this adjustment was not balanced by corresponding requirements that humanities students enroll in introductory science courses. These questions of academic focus have continued to be a source of debate, as universities continually struggle to balance their arts versus science programs.
Postdoctoral researcher Dr. Stefano Tiziani (left) and Dr. Giovanni Paternostro, adjunct assistant professor at Sanford-Burnham, in the NMR facility
Genomics is a global look at all the DNA or genes in a cell or organism and proteomics refers to all the proteins. But these don’t necessarily tell the whole story about what’s going on inside a cell at a given moment. Metabolomics adds another layer of complexity, describing all the chemical reactions a cell uses to process nutrients and produce both energy and the chemical building blocks required for maintenance and growth.
Since cellular metabolism relies on an intricate and finely-tuned network of interconnected pathways involving many proteins and enzymes, it follows that many human diseases, including cancer, can throw metabolism off, changing the relative abundance of different metabolites (the chemicals involved in metabolism). Thus, the ability to detect and quantify such metabolic changes would make a very useful tool for evaluating the status of a disease and judging the effectiveness of a therapy.
Even though a large portion of the research work at Sanford-Burnham historically has been carried out by postdoctoral trainees, graduate students have always had a presence at the Institute. In the past, these individuals were officially enrolled at UC San Diego or other universities and carried out their research in a lab at Sanford-Burnham because of its particular expertise. Although this type of arrangement still continues, the situation changed in 2006 when the Institute founded its own graduate training program designed to confer Ph.D. degrees. The Graduate School of Biomedical Sciences at Sanford-Burnham was recently recognized by the Western Association of Schools and Colleges (WASC) as a Candidate for Accreditation.*
According to the Dean of the program, Dr. Guy Salvesen, “Our eventual goal of full accreditation will serve as proof of what we already know; namely, that a Ph.D. degree from the Institute is a rigorous one of high quality that stacks up well against a degree from any of the other outstanding institutions that students might choose.”
Dr. Malene Hansen (right), pictured here with graduate student Philip McQuary, emphasizes the importance of mentoring during the postdoctoral training years. (Photo by Nadia Borowski Scott)
In theory, our system of advanced science education is designed to move students through graduate school and then postdoctoral training en route to taking their places as principal investigators (PIs) heading their own research laboratories. In reality, even in past years there were clearly more scientists being trained than there were openings for lab heads and faculty positions. To some extent this bottleneck was alleviated over the past two decades by the boom in the biotechnology industry, which has offered an outside-of-academia source of jobs for trained scientists. However, the slumping economy has hit the biotech industry just as hard as everyone else, with downsizing taking a large bite out of available industrial jobs. And now, with competition for grant funding more intense than ever and academic job opportunities increasingly scarce, postdoctoral researchers often feel that they are in a holding pattern waiting for the occasional faculty or industrial position to open up. How can postdocs deal most effectively with this situation in terms of preparing themselves to compete for rare openings?
On July 28, the Sanford-Burnham Science Network (SBSN), an organization of postdocs and graduate students, sponsored a discussion of the tricky transition from postdoc to PI. The session was chaired by SBSN leaders Dr. Caroline Kumsta and Dr. Rachel Wilkie, both postdocs at the Institute. Dr. Malene Hansen and Dr. Stefan Riedl, two young Sanford-Burnham faculty members, led the discussion by sharing their own steps leading from postdoctoral researcher to assistant professor.
Microscope available in Sanford-Burnham's Cell Imaging facility
Editor’s note: This is the first in a series of posts highlighting Shared Resources available at Sanford-Burnham. Future posts will further explore some of the individual capabilities found in these core facilities.
Suppose you’re a new assistant professor just starting your career at Sanford-Burnham, and you need to perform some high-resolution fluorescence microscopy to finish your first big paper as a principal investigator. How do you afford that $400,000 confocal microscope for the key experiments? For that matter, how does anyone afford a $400,000 microscope? Here’s where Shared Resources saves the day. Just down the stairway sits the Zeiss Laser Scanning Confocal Microscope that Sanford-Burnham’s Cell Imaging facility has thoughtfully provided for you. How did you get so lucky?
Dr. Mihee Kim, new postdoc in Dr. Robert Oshima's lab
Editor’s note: We often hear how important it is to make a good first impression. We thought it would be interesting to learn about newcomers’ first impressions of Sanford-Burnham, so we interviewed some new employees who each play a different role at the Institute’s La Jolla campus.
One of our most recent employees, Dr. Mihee Kim, has been a postdoctoral associate in Dr. Robert Oshima’s lab since June of this year. From previous positions at Harvard and NIH, Mihee had experience both with stem cells and with proteins that bind to nucleic acids (such as DNA). She is combining those disciplines in the Oshima lab’s attempt to understand the role of the Ets2 transcription factor (a protein that controls the expression of other genes) in the behavior of cancer stem cells. Mihee had heard of Sanford-Burnham because a former Harvard colleague, Dr. Dieter Wolf, took a position as professor here in 2007. She had no preconceived impressions of the Institute, but has been pleased to learn that our claims of having a collaborative culture are not overstated. Being somewhat new to working with animal models, Mihee has already established interactions with postdocs in several Institute labs to develop a robust system for identifying intestinal stem cells. She has also found the imaging and flow cytometry shared services to be very effective resources for interaction and for providing both training and expert analysis.
Most amazing, she says, is the fact that, “people actually respond in a helpful way to e-mail requests for advice and reagents. I never had that experience before!”
Mihee is excited about the freedom she has been given by Dr. Oshima to explore multiple aspects of Ets2/cancer stem cell function according to her own curiosity and intuition.
Stephen Hawking, famous English physicist, lives with amyotrophic lateral sclerosis (Lou Gehrig's disease), a debilitating disese that affects motor neurons.
Many people are familiar with the story of Alexander Fleming’s accidental discovery of penicillin produced by mold growing in a bacterial culture. These same people would probably be surprised at how often carefully planned scientific experiments yield unexpected (and even unwanted!) results, usually leading to repetition of the experiment to discover where things went wrong. However, one mark of a really good investigator (like Fleming) is the ability to recognize when the “error” may actually be a truth that provides a key new insight. The phenomenon of looking for one thing and serendipitously finding another plays a surprisingly frequent role in the process of scientific discovery.
A case in point can be found in studies of motor neuron degeneration being carried out in the laboratory of Dr. Dongxian Zhang, associate professor at Sanford-Burnham. The death of motor neurons in the spinal cord is responsible for lethal diseases such as spinal muscular atrophy and amyotropic lateral sclerosis (Lou Gehrig’s disease), neither of which is treatable or curable. Dr. Zhang’s group hypothesized that motor neuron death might be caused by the absence or malfunction of a specific type of membrane receptor called MNR. To test their theory more directly, they paid a commercial company to create a mouse in which MNR was genetically deleted. Sure enough, motor neurons in these mice degenerated a few days after birth. To further prove their point, the group attempted to rescue the lethal defect by genetically adding back the MNR gene. To their consternation, these transgenic rescue mice still died shortly after birth.
“At that point we were completely stumped and discouraged,” confesses Dr. Zhang.
In the movie Extraordinary Measures, Harrison Ford plays a glycobiologist.
Earlier this summer, Dr. Hudson Freeze, program director in Sanford-Burnham’s Sanford Children’s Health Research Center, chaired the Gordon Conference on Glycobiology in Lucca, Italy. 170 glycobiologists from around the world gathered to hear about exciting new developments in the science of carbohydrates (sugar molecules) and the complex molecules like proteins and lipids whose properties are influenced by incorporation of carbohydrates. Once a rather understudied area of biology, glycobiology has been transformed by the realization that carbohydrates mediate many of the key molecular interactions that govern cellular function. Meeting topics included the effects of sugar modifications during development, the role of carbohydrates in normal adult physiology and the involvement of carbohydrates in tissue engineering and repair, including their importance in stem cell biology.
iRGD peptides can specifically target cancer drugs (red) to the blood vessels that feed tumors (green). (Image courtesy of Kazuki
At a time when scientists are having increasing difficulty acquiring financial support from federal sources, alternative sources of funding are becoming more important for maintaining the momentum of critical research at universities, research institutes and even industrial laboratories. At Sanford-Burnham, research assistant professor Dr. Kazuki N. Sugahara was recently awarded a one-year, $75,000 grant from The San Diego Foundation, via the The Blasker-Rose-Miah Fund. This marks one of the few times that a Sanford-Burnham investigator has received funding from this source, underscoring the novelty and importance of the project. This key piece of local funding will allow Dr. Sugahara to continue his research on the use of tissue-penetrating peptides that can detect developing tumors and enhance the delivery of cancer therapeutic drugs.