Limits...
A question of taste.

Mitchison TJ - Mol. Biol. Cell (2013)

Bottom Line: These typically form early and are shaped by subsequent successes and failures.I will try to identify where they came from, how they shaped my career, and how they continue to evolve.My hope is to inspire young scientists to identify and celebrate their own unique tastes.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115.

ABSTRACT
A career in science is shaped by many factors, one of the most important being our tastes in research. These typically form early and are shaped by subsequent successes and failures. My tastes run to microscopes, chemistry, and spatial organization of cytoplasm. I will try to identify where they came from, how they shaped my career, and how they continue to evolve. My hope is to inspire young scientists to identify and celebrate their own unique tastes.

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My taste in molecules. (A) The remarkable dynamics of tubulin. This graph shows microtubule growth rate as a function of soluble tubulin concentration. Microtubules shrink much faster than expected from extrapolating their growth rate to zero tubulin, because GTP hydrolysis destabilizes them. (Adapted from Mitchison and Kirschner, 1984.) (B) Caged fluorescein, used to measure microtubule sliding in mitotic spindles (Mitchison, 1989). The sulfo-NHS ester portion at the bottom is for labeling lysine residues. (C) Monastrol, the first small-molecule inhibitor of kinesin-5 (also known as Eg5, KSP, and Kif11; Mayer et al., 1999). (D) DMXAA, a drug that was effective for cancer treatment in mice but not humans. We and others recently found that it is a mouse STING agonist (Conlon et al., 2013; Kim et al., 2013). The normal function of STING is to activate an innate immune response to DNA or bacteria in the cytoplasm (reviewed in Paludan and Bowie, 2013).
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Figure 1: My taste in molecules. (A) The remarkable dynamics of tubulin. This graph shows microtubule growth rate as a function of soluble tubulin concentration. Microtubules shrink much faster than expected from extrapolating their growth rate to zero tubulin, because GTP hydrolysis destabilizes them. (Adapted from Mitchison and Kirschner, 1984.) (B) Caged fluorescein, used to measure microtubule sliding in mitotic spindles (Mitchison, 1989). The sulfo-NHS ester portion at the bottom is for labeling lysine residues. (C) Monastrol, the first small-molecule inhibitor of kinesin-5 (also known as Eg5, KSP, and Kif11; Mayer et al., 1999). (D) DMXAA, a drug that was effective for cancer treatment in mice but not humans. We and others recently found that it is a mouse STING agonist (Conlon et al., 2013; Kim et al., 2013). The normal function of STING is to activate an innate immune response to DNA or bacteria in the cytoplasm (reviewed in Paludan and Bowie, 2013).

Mentions: I was inspired to join Kirschner's lab at the University of California, San Francisco (UCSF), after hearing Kirschner give a series of lectures on space and time in biology. I felt then, and still do, that he aims at principles, although getting there entails a lot of wading through details. I chose to work on centro­somes, hoping they might be the brain of the cytoplasm, but our immediate goals were to purify them and figure out how they nucleate microtubules. This nucleation problem lies at the heart of cell organization and is still unsolved, although we probably do know the major protein players. I succeeded in purifying centrosomes, but the technologies then available were too insensitive to identify their components. Somewhat in desperation, I turned to study the assay I had been using, and ended up discovering dynamic instability, wherein individual microtubules exhibit large length fluctuations powered by GTP hydrolysis (Mitchison and Kirschner, 1984). This discovery defined my subsequent career and my taste in subsequent research. “You can always get a paper out of your assay” is something I tell students to this day. It came from analyzing individual microtubules, rather than average behavior, which was natural, given my taste for microscopy, but the key innovation was to freeze the tubulin in tiny aliquots. Every time I thawed one, it behaved the same way, so I could make measurements on multiple days and plot them on the same graph (Figure 1A). I think I learned that from Bruce Alberts. He favored 50% glycerol stocks at −20°C but drilled into me the idea that, if you are careful with your proteins, they will reward you with consistent and interesting behavior. Measuring individuals rather than averages turns out to be generally good taste. Systems biology, my current departmental affiliation, has prospered by quantifying the dynamics of individual cells, which is often more interesting than the population average.


A question of taste.

Mitchison TJ - Mol. Biol. Cell (2013)

My taste in molecules. (A) The remarkable dynamics of tubulin. This graph shows microtubule growth rate as a function of soluble tubulin concentration. Microtubules shrink much faster than expected from extrapolating their growth rate to zero tubulin, because GTP hydrolysis destabilizes them. (Adapted from Mitchison and Kirschner, 1984.) (B) Caged fluorescein, used to measure microtubule sliding in mitotic spindles (Mitchison, 1989). The sulfo-NHS ester portion at the bottom is for labeling lysine residues. (C) Monastrol, the first small-molecule inhibitor of kinesin-5 (also known as Eg5, KSP, and Kif11; Mayer et al., 1999). (D) DMXAA, a drug that was effective for cancer treatment in mice but not humans. We and others recently found that it is a mouse STING agonist (Conlon et al., 2013; Kim et al., 2013). The normal function of STING is to activate an innate immune response to DNA or bacteria in the cytoplasm (reviewed in Paludan and Bowie, 2013).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3814136&req=5

Figure 1: My taste in molecules. (A) The remarkable dynamics of tubulin. This graph shows microtubule growth rate as a function of soluble tubulin concentration. Microtubules shrink much faster than expected from extrapolating their growth rate to zero tubulin, because GTP hydrolysis destabilizes them. (Adapted from Mitchison and Kirschner, 1984.) (B) Caged fluorescein, used to measure microtubule sliding in mitotic spindles (Mitchison, 1989). The sulfo-NHS ester portion at the bottom is for labeling lysine residues. (C) Monastrol, the first small-molecule inhibitor of kinesin-5 (also known as Eg5, KSP, and Kif11; Mayer et al., 1999). (D) DMXAA, a drug that was effective for cancer treatment in mice but not humans. We and others recently found that it is a mouse STING agonist (Conlon et al., 2013; Kim et al., 2013). The normal function of STING is to activate an innate immune response to DNA or bacteria in the cytoplasm (reviewed in Paludan and Bowie, 2013).
Mentions: I was inspired to join Kirschner's lab at the University of California, San Francisco (UCSF), after hearing Kirschner give a series of lectures on space and time in biology. I felt then, and still do, that he aims at principles, although getting there entails a lot of wading through details. I chose to work on centro­somes, hoping they might be the brain of the cytoplasm, but our immediate goals were to purify them and figure out how they nucleate microtubules. This nucleation problem lies at the heart of cell organization and is still unsolved, although we probably do know the major protein players. I succeeded in purifying centrosomes, but the technologies then available were too insensitive to identify their components. Somewhat in desperation, I turned to study the assay I had been using, and ended up discovering dynamic instability, wherein individual microtubules exhibit large length fluctuations powered by GTP hydrolysis (Mitchison and Kirschner, 1984). This discovery defined my subsequent career and my taste in subsequent research. “You can always get a paper out of your assay” is something I tell students to this day. It came from analyzing individual microtubules, rather than average behavior, which was natural, given my taste for microscopy, but the key innovation was to freeze the tubulin in tiny aliquots. Every time I thawed one, it behaved the same way, so I could make measurements on multiple days and plot them on the same graph (Figure 1A). I think I learned that from Bruce Alberts. He favored 50% glycerol stocks at −20°C but drilled into me the idea that, if you are careful with your proteins, they will reward you with consistent and interesting behavior. Measuring individuals rather than averages turns out to be generally good taste. Systems biology, my current departmental affiliation, has prospered by quantifying the dynamics of individual cells, which is often more interesting than the population average.

Bottom Line: These typically form early and are shaped by subsequent successes and failures.I will try to identify where they came from, how they shaped my career, and how they continue to evolve.My hope is to inspire young scientists to identify and celebrate their own unique tastes.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115.

ABSTRACT
A career in science is shaped by many factors, one of the most important being our tastes in research. These typically form early and are shaped by subsequent successes and failures. My tastes run to microscopes, chemistry, and spatial organization of cytoplasm. I will try to identify where they came from, how they shaped my career, and how they continue to evolve. My hope is to inspire young scientists to identify and celebrate their own unique tastes.

Show MeSH
Related in: MedlinePlus