Sharing MCB Science: Learning Much More about Spores

Like all living organisms, bacteria need nutrients in their environment to survive and grow. When the survival of bacteria like Bacillus subtilis is threatened by starvation they respond by going into a “hibernation” state by forming spores. The process for producing a spore, called sporulation, is highly complex and requires careful coordination with other cellular processes like DNA replication. To understand how cells are able to orchestrate this coordination, Dr. Oleg Igoshin, an Associate Professor at Rice University partnered with Associate Professor, Gurol Suel from the University of California San Diego to study sporulation of the soil bacterium Bacillus subtilis, a model organism for systems biology research.

Jatin Narula, Anna Kuchina, Dong-Yeon D. Lee, and Masaya Fujita compose the research team, led by Igoshin and Suel, interested in clarifying the genetic mechanism of spore formation or sporulation. By combining experimental methods from systems and synthetic biology with mathematical modeling, the researchers uncovered the coordination mechanism required for sporulation. The modeling predicted that the key to this coordination is the specific arrangement of two pivotal sporulation genes on the bacterial chromosome. This arrangement produces a temporary mismatch in the number of copies of these two genes during DNA replication. This mismatch is detected by the biochemical network controlling sporulation to ensure proper coordination and the completion of DNA replication. These predictions were confirmed when rearrangement of the two pivotal genes on the chromosome prevented cells from sporulating. The sporulation mechanism that Igoshin and his team elucidated is described in the video above and in a recent research article in Cell.

When asked about the broader impacts of this research for cell biology, Igoshin said “We found that the relative arrangement of the two sporulation genes on DNA were similar in more than 40 strains of spore-forming bacteria. This evidence suggests that this timing mechanism is highly conserved, and it is possible that other time-critical functions related to the cell cycle may be regulated in a similar way.”

In addition to the scientific impact of this research, the collaborative nature of the research provided interdisciplinary training for participating graduate students. Furthermore, the innovative approaches used by Igoshin and colleagues may be applicable to similar problems in other organisms and useful for teaching system-level concepts to students of various levels and backgrounds.

Principal Investigator Spotlight: Dr. Sandra Murray

Tell Us about Your Current Career Position and Your Research Focus.

I am currently a Professor in the Department of Cell Biology at the University of Pittsburgh where I am working to elucidate the molecular mechanisms that regulate gap junction plaque assembly, disassembly, and degradation.

What Are the Key Experiences and Decisions You Made That Have Helped You Reach Your Current Position?

My early opportunities to get involved in science fairs while still in grammar school opened the door to a number of opportunities which led me outside my immediate community and facilitated my meeting a diverse group of mentors, getting into summer programs, gaining employment while in College and eventually getting into my chosen field.

One of my high school science fair projects resulted in my being identified by a biology teacher to participate in a science program at the University of Chicago during the academic year. As part of that program, I spent the summer in the Department of Anatomy at the University of Illinois, School of Medicine. My job was to clean the medical school students’ histology slides by wiping them with an alcohol-soaked towel. The slides were covered with immersion oil that needed to be removed in preparation for use by the next class of medical students. I took this task very seriously. Innovative at an early age, I decided to dump all the slides in a large glass container filled with alcohol overnight to soak so that then the next morning I would only have to wipe the slides dry and return them to the correct slots in the boxes (all slides were labeled by box and slot number). When I arrived the next morning, the debris was gone from the slides but to my horror, almost all the labels had soaked off as well. I decided I would tell the head technician what had happened, but that it would be best to wait until I had repaired the damage before asking for help. After all, my mother had told half the neighborhood that her little daughter was working at the University. How the heck could I tell them I had been fired after only a week? Better to try to repair the problem, prolong the summer job, and then tell them, I decided. For the next weeks, I came in early to make the new labels and to try to match the unlabeled slides to the slides in the box that I had not dumped for soaking. I held the slides to the light and matched by color of the stain, size of the specimen, and perhaps a good guess. Finally however I asked a young research scientist to check if my identifications were correct. I expected him to hold the slide to the light and make the magical judgment call, “this is a slice of liver.” Instead, he immediately went to the large microscope sitting on a table in the corner. A world opened for me that day!!!! Who knew the power of that thing in the corner that I had ignored until now? Wow. I was hooked!!!  I used the microscope to reorganize my earlier guesses. I arrived earlier and stayed later than the head histologist, in order to re-label and restore the slides to the correct slots in a box. The chairman of the department took notice of my diligence (my frantic attempt to recover from my mistake and to restore the boxes) and he was amazed at the now sparkling slides (soaked, polished untill they glittered, and newly labeled). When the summer program ended, not only did I not get fired for my innovative mishap with the slides, but instead I was hired by that chairman to work in the Department of Anatomy during Christmas breaks and following summers.

I have continued throughout my career to use microscopes.  Now, I couple the visual observations made with microscopes to biochemical and molecular biological observations made with the new tools of science to answer questions.

Did Support from the Division of Molecular and Cellular Biosciences Impact Your Research And/or Career? If So, Then How?

Support from the Division of Molecular and Cellular Bioscience has permitted my research team to demonstrate the increase in gap junction channels following treatment of cells with certain hormones, the inverse relationship between cell proliferation and gap junction channels, the molecules that move through the channels, the function of these molecules once they move through the gap junction channels and most recently the molecular machinery and processing needed for the removal of gap junction channels from the cell surface and subsequent degradation.The world of gap junctions and cell-cell communication has blossomed and funding from the NSF has allowed me to be part of the team that has planted, tilled and watched as the field continues to grow.

Beyond the scientific impact that NSF funding has allowed, my career has been greatly enhanced. Without funding from the Division of Molecular and Cellular Biosciences, I would not have been able to  lead a research team or provide training and opportunities to others who have excelled in science.

How Did You First Become Interested in Science?

My science projects took me many places. I made hard water soft with one of my science entries and my mother took me to a water company where they could give me tips on making my contraption and my father helped me assemble my design from parts left over in our moving company (Murray Brothers Movers) garage. The project was a bust and did not win anything but it left me eager for the next science adventure. I tried to slow the growth of little creatures called Rotifers. My older sister took me to the University of Illinois and to the VA hospital to get agar plates for me to dabble into bacteriology and by the time I left grade school, my entire family and some members of the neighborhood has assisted me in my path toward discovery.

What Is it That Keeps You Working Hard and Engaged in Your Work?

I want to see more! I want to find out why? I really like what I do. I enjoy watching while the next generation of scientists discovers a world that only few get to see.

Were There Times When You Failed at Something You Felt Was Critical to Your Path? If So, Then How Did You Regroup and Get Back on Track?

Failure was a part of the game. I try to do my own personal best and to maintain my own internal standards. I understood early on that I did not have to be the best at everything, but that I had to focus on certain areas. I found that sometimes things were difficult and participating in those things was not comfortable, but if I took on the difficult task (one little step at a time) then I would grow. For example, I was a very shy person and it was truly a struggle to stand and speak to group. Public speaking is critical to being able to present data at scientific meetings and teach at the University. I shook each time I walked toward a podium. But each time I presented, it became a bit easier. Today, I look forward to the opportunity to speak and to bring my message to the audience. Failure and difficult times have taught me how to understand and treat other people, as well as how to just get up from a fall.

What Advice Would You Give to Others Who Want to Pursue a Career in Science That Is Similar to Yours?

Set clear goals; visualize where you want to go and what you want to do. Let your mind wander to tap into your own power, and manage your time so that you can climb your academic mountains and realize your dreams.

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Congratulations to 2014 Nobel Laureate, William E. Moerner

Congratulations to MCB Principal Investigator William E. Moerner on being awarded a 2014 Nobel Prize in Chemistry!  Moerner is one of three recipients whose research on “the development of super-resolved fluorescence microscopy” has transformed the field of nanoscopy, a method used to visualize single molecules and their activity within cells.  His work in Surpassing the limitations of the Light Microscope was supported by the Molecular Biophysics Cluster in 1999.

MCB proudly recognizes the investments made into Dr. Moerner and his research as his work has made profound impacts on the progress of science.

Click here to hear his response below.