Research

On September 1st I started a lab in the MIT physics department.  Please go to that page for up-to-date information on my research.

I was a Pappalardo Fellow in the physics department at MIT (with additional funding from an NIH K99 Pathways to Independence Award).  I worked in the group of Alexander van Oudenaarden, studying the evolution of cooperation using sucrose metabolism in yeast as a model system . 

My graduate work was in single-molecule biophysics in the department of physics at the University of California at Berkeley with Professor Carlos Bustamante in collaboration with Professor Nicholas Cozzarell (summary of my graduate research).

Before finding my way to biophysics, I spent my first year at Berkeley with Professor Paul McEuen demonstrating that an electrolyte can efficiently gate a single-walled carbon carbon nanotube transister (pdf).  As an undergrad at MIT I wrote my undergraduate thesis with Professor Wolfgang Ketterle on Bose-Einstein Condensation (BEC).

Summary of Postdoctoral Research (abstract from qBio conference, pdf)

The evolution of cooperation presents a significant challenge to our understanding of evolution [1,2]. If evolution favors survival of the fittest, then how can costly behaviors that benefit others arise? 

The simple monosaccharides glucose and fructose are the preferred carbon sources of the budding yeast S. cerevisiae, although when these sugars are not available yeast can utilize alternative carbon sources such as sucrose [3], a disaccharide composed of glucose and fructose. Digesting sucrose requires that the disaccharide be broken down into its constituent sugars, a reaction catalyzed by the enzyme invertase which is secreted into the periplasmic space between the plasma membrane and the cell wall [4]. However, it may be possible for some of the resulting glucose and fructose to diffuse away before the cell is able to import them. Supporting the idea that monosaccharide loss to the environment may be important, it has been shown that at high density on a sucrose plate a “cheater” strain with the invertase gene knocked out is able to outcompete the wildtype strain [5].

I.RESULTS

We have found that the growth rate of yeast in sucrose culture increases with cell density, suggesting that sucrose metabolism is indeed cooperative. After invertase hydrolyzes sucrose at the cell surface there is a competition between monosaccharide import and diffusion away from the cell. Analytical calculations predict that only ~1% of the monosaccharides are captured; the vast majority of the glucose and fructose therefore diffuse away and are eventually consumed by other cells. Experimental measurements of the rate of sucrose hydrolysis and monosaccharide import quantitatively validate these theoretical predictions and provide a framework through which to understand the nature of cooperation in this system.  The production and secretion of invertase is a cooperative behavior with a leaky capture of benefits (in this case monosaccharide import).

We have developed a simple game theory model that yields a phase diagram predicting the outcome of competition between wildtype cooperator cells and mutant cheater cells lacking the invertase gene. We are able to probe this phase diagram experimentally by controlling both the sugar concentrations and the cost of cooperation (using a histidine auxotroph cooperator together with limiting histidine concentrations). As the parameters governing the interaction are varied we are able to transform the nature of the “game” and observe qualitatively different experimental outcomes—either coexistence of the two strains or extinction of the cooperating strain. However, over a wide range of parameters we observe coexistence between the cooperator and cheater strains, suggesting that the interaction is a snowdrift game in which the optimal strategy is the opposite of one’s opponents [2]. Finally, we have experimentally characterized the wildtype invertase production strategy and find that the response is appropriate for the snowdrift game—wildtype cells cooperate when competing against cheater cells but cheat when competing against cells that always cooperate.

II.CONCLUSION

This study demonstrates how a given cooperative interaction—in this case a leaky capture of benefits—can lead to qualitatively different outcomes depending upon the conditions of the competition. In the future we plan to extend these experiments to consider competition in spatially structured environments.

REFERENCES

[1]Axelrod, R. and W.D. Hamilton, The Evolution of Cooperation. Science, 1981. 211(4489): p. 1390-1396.

[2]Nowak, M.A., Five rules for the evolution of cooperation. Science, 2006. 314(5805): p. 1560-1563.

[3]Gancedo, J.M., Yeast carbon catabolite repression. Microbiology and Molecular Biology Reviews, 1998. 62(2): p. 334-+.

[4]Carlson, M. and D. Botstein, 2 Differentially Regulated Messenger-Rnas with Different 5' Ends Encode Secreted and Intracellular Forms of Yeast Invertase. Cell, 1982. 28(1): p. 145-154.

[5]Greig, D. and M. Travisano, The Prisoner's Dilemma and polymorphism in yeast SUC genes. Proceedings of the Royal Society of London Series B-Biological Sciences, 2004. 271: p. S25-S2.

Publications

Snowdrift game dynamics and facultative cheating in yeast

Jeff Gore, Hyun Youk, and Alexander van Oudenaarden

Nature (2009)

Media: Tech Talk article

The yin and yang of nature [News & Views]

Jeff Gore and Alexander van Oudenaarden

Nature 457, 271 - 272 (2009)

Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torque

Marcelo Nollmann, Michael D. Stone, Zev Bryant, Jeff Gore, Seok-cheol Hong, Nancy J. Crisona,Sylvain Mitelheiser, Anthony Maxwell, Carlos Bustamante, and Nicholas Cozzarelli

Nature Structural and Molecular Biology 14, 264 - 271 (2007)

News & Views:  Under DNA stress, gyrase makes the sign of the cross, Pat Higgins, NSMB.

DNA overwinds when stretched

Jeff Gore, Zev Bryant, Marcelo Nollmann, Mai U. Le, Nicholas R. Cozzarelli, and Carlos Bustamante

Nature 442, 836 - 839 (2006)

Mechanochemical analysis of DNA gyrase using rotor bead tracking

Jeff Gore, Zev Bryant, Michael D. Stone, Marcelo Nollmann, Nicholas R. Cozzarelli, and Carlos Bustamante

Nature 439, 100 - 104 (2006)

Identification of oligonucleotide sequences that direct the movement of the Escherichia coli translocase FtsK

Oren Levy, Jerod L. Ptacin, Paul J. Pease, Jeff Gore, Michael B. Eisen, Carlos Bustamante, and Nicholas R. Cozzarelli.

Proc. Natl. Acad. Sci. 102, 17618 - 17623 (2005)

Sequence-Directed DNA Translocation by Purified FtsK.

Paul J. Pease, Oren Levy, Gregory J. Cost, Jeff Gore, Jerod L. Ptacin, David Sherratt, Carlos Bustamante, and Nicholas R. Cozzarelli. 

Science  307, 586 - 590 (2005)

Hanging around at dif

Angela K Eggleston.  News & Views on the FtsK paper above.

Nature Structural and Molecular Biology 12, 216 (2005)

Bias and error in estimates of equilibrium free-energy differences from nonequilibrium measurements.

Jeff Gore, Felix Ritort, and Carlos Bustamante. 

Proc. Natl. Acad. Sci. 100, 12564 (2003)

Using nonequilibrium measurements to determine macromolecule free-energy differences

Ronald F. Fox. PNAS Commentary on the paper above:  

PNAS 100, 12537 (2003).

Structural transitions and elasticity from torque measurements on DNA.

Zev Bryant, Michael D. Stone, Jeff Gore, Steven B. Smith, Nicholas R. Cozzarelli, Carlos Bustamante. 

Nature 424, 338 (2003)

High Performance Electrolyte Gated Carbon Nanotube Transistors.

Sami Rosenblatt, Yubal Yaish, Jiwoong Park, Jeff Gore, Vera Sazonova, and Paul McEuen. 

Nano Letters. 2, 8 (2002)

Construction and implementation of NMR quantum logic gates for two spin systems,

M.D. Price, S.S. Somaroo, C.H. Tseng, J.C. Gore, A.F. Fahmy, T.R. Havel, and D.G. Cory. 

Journal of Magnetic Resonance. 140: 371 - 378 (1999)