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Papers by Joseph Graves Jr

Research paper thumbnail of Why We Must Teach Our Students about Race

The American Biology Teacher

Research paper thumbnail of People, We Have a Problem: Comment

Anesthesiology, Aug 8, 2023

Research paper thumbnail of Bacteriophages and viruses (not alive, but important)

Research paper thumbnail of What Darwin never saw: how things differ between the microbial and macroscopic world. (Horizontal gene transfer, co-selection, persister cells)

Research paper thumbnail of Fruit Fly Aging and Mortality

Science, Jun 11, 1993

Published by the American Association for the Advancement of Science (AAAS), Science serves its r... more Published by the American Association for the Advancement of Science (AAAS), Science serves its readers as a forum for the presentation and discussion of important issues related to the advancement of science, including the presentation of minority or conflicting points of view, rather than by publishing only material on which a consensus has been reached. Accordingly, all articles published in Science-including editorials, news and comment, and book reviews-are signed and reflect the individual views of the authors and not official points of view adopted by the AAAS or the institutions with which the authors are affiliated.

Research paper thumbnail of Co-adaptation of Streptococcus mutans to simulated microgravity and silver nitrate

Frontiers in Astronomy and Space Sciences, Jun 15, 2023

To sustain life on extended space missions, it is essential to maintain clean potable water. NASA... more To sustain life on extended space missions, it is essential to maintain clean potable water. NASA currently uses iodine as the primary biocide in the potable water dispenser on the International Space Station and has recently proposed a potential switch to silver-based antimicrobials. Streptococcus mutans is the primary etiological agent of dental caries, part of the normal oral flora, and would endure direct exposure to water from the potable water dispenser. In our previous work, we examined the 100-day adaptive response of Streptococcus mutans to simulated microgravity (sMG). Here, we examined the evolutionary co-adaptation of S. mutans under sMG and silver nitrate (AgNO3) to evaluate the consequences of using silver as a primary biocide in space and the impact on the evolution of microbes from the oral microbiome. To do this, we adapted four populations of S. mutans under sMG and co-adapted four populations in simulated microgravity and silver nitrate using high-aspect ratio vessels for 100 days. Genomic analysis at multiple time points showed that S. mutans in sMG evolved variants consistent with our previous findings (SMU_1307c and SMU_399) while also acquiring novel mutations in the glutathione reductase gorA. The co-adapted populations showed mutations specific for the environment in ciaH/R, PBP1a, trkA, and trkB. We also assessed virulence phenotypes, and while simulated microgravity increased antibiotic susceptibility, sucrose-dependent adhesion, and, in some populations, acid tolerance, co-adaptation to silver nitrate reversed these effects. Overall, these data show that the use of silver as a biocide in simulated microgravity can evolve strains with novel genotypic and phenotypic traits that could alter virulence.

Research paper thumbnail of Inequality in science and the case for a new agenda

Proceedings of the National Academy of Sciences of the United States of America, Feb 24, 2022

The history of the scientific enterprise demonstrates that it has supported gender, identity, and... more The history of the scientific enterprise demonstrates that it has supported gender, identity, and racial inequity. Further, its institutions have allowed discrimination, harassment, and personal harm of racialized persons and women. This has resulted in a suboptimal and demographically narrow research and innovation system, a concomitant limited lens on research agendas, and less effective knowledge translation between science and society. We argue that, to reverse this situation, the scientific community must reexamine its values and then collectively embark upon a moonshot-level new agenda for equity. This new agenda should be based upon the foundational value that scientific research and technological innovation should be prefaced upon progress toward a better world for all of society and that the process of how we conduct research is just as important as the results of research. Such an agenda will attract individuals who have been historically excluded from participation in science, but we will need to engage in substantial work to overcome the longstanding obstacles to their full participation. We highlight the need to implement this new agenda via a coordinated systems approach, recognizing the mutually reinforcing feedback dynamics among all science system components and aligning our equity efforts across them.

Research paper thumbnail of Experimental evolution of gallium resistance in Escherichia coli

Evolution, medicine & public health, 2019

Background and Objectives: Metallic antimicrobial materials are of growing interest due to their ... more Background and Objectives: Metallic antimicrobial materials are of growing interest due to their potential to control pathogenic and multidrug-resistant bacteria. Yet we do not know if utilizing these materials can lead to genetic adaptations that produce even more dangerous bacterial varieties. Methodology: Here we utilize experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to, the iron analog, gallium nitrate (Ga(NO 3) 3). Whole genome sequencing was utilized to determine genomic changes associated with gallium resistance. Computational modeling was utilized to propose potential molecular mechanisms of resistance. Results: By day 10 of evolution, increased gallium resistance was evident in populations cultured in medium containing a sublethal concentration of gallium. Furthermore, these populations showed increased resistance to ionic silver and iron (III), but not iron (II) and no increase in traditional antibiotic resistance compared with controls and the ancestral strain. In contrast, the control populations showed increased resistance to rifampicin relative to the gallium-resistant and ancestral population. Genomic analysis identified hard selective sweeps of mutations in several genes in the gallium (III)-resistant lines including: fecA (iron citrate outer membrane transporter), insl1 (IS30 tranposase) one intergenic mutations arsC !/! yhiS; (arsenate reductase/pseudogene) and in one pseudogene yedN ; (iapH/yopM family). Two additional significant intergenic polymorphisms were found at frequencies > 0.500 in fepD /! entS (iron-enterobactin transporter subunit/enterobactin exporter, iron-regulated) and yfgF /! yfgG (cyclic-di-GMP phosphodiesterase, anaerobic/uncharacterized protein). The control populations displayed mutations in the rpoB gene, a gene associated with rifampicin resistance. Conclusions: This study corroborates recent results observed in experiments utilizing pathogenic Pseudomonas strains that also showed that Gram-negative bacteria can rapidly evolve resistance to original research article

Research paper thumbnail of Genomic evolution of antibiotic resistance is contingent on genetic background following a long-term experiment with <i>Escherichia coli</i>

Proceedings of the National Academy of Sciences of the United States of America, Jan 13, 2021

Antibiotic resistance is a growing health concern. Efforts to control resistance would benefit fr... more Antibiotic resistance is a growing health concern. Efforts to control resistance would benefit from an improved ability to forecast when and how it will evolve. Epistatic interactions between mutations can promote divergent evolutionary trajectories, which complicates our ability to predict evolution. We recently showed that differences between genetic backgrounds can lead to idiosyncratic responses in the evolvability of phenotypic resistance, even among closely related Escherichia coli strains. In this study, we examined whether a strain's genetic background also influences the genotypic evolution of resistance. Do lineages founded by different genotypes take parallel or divergent mutational paths to achieve their evolved resistance states? We addressed this question by sequencing the complete genomes of antibiotic-resistant clones that evolved from several different genetic starting points during our earlier experiments. We first validated our statistical approach by quantifying the specificity of genomic evolution with respect to antibiotic treatment. As expected, mutations in particular genes were strongly associated with each drug. Then, we determined that replicate lines evolved from the same founding genotypes had more parallel mutations at the gene level than lines evolved from different founding genotypes, although these effects were more subtle than those showing antibiotic specificity. Taken together with our previous work, we conclude that historical contingency can alter both genotypic and phenotypic pathways to antibiotic resistance.

Research paper thumbnail of Science, Empire, and Imperialism

Routledge eBooks, Oct 19, 2022

Research paper thumbnail of Adaptation to simulated microgravity in Streptococcus mutans

NPJ microgravity, Jun 2, 2022

Long-term space missions have shown an increased incidence of oral disease in astronauts' and as ... more Long-term space missions have shown an increased incidence of oral disease in astronauts' and as a result, are one of the top conditions predicted to impact future missions. Here we set out to evaluate the adaptive response of Streptococcus mutans (etiological agent of dental caries) to simulated microgravity. This organism has been well studied on earth and treatment strategies are more predictable. Despite this, we are unsure how the bacterium will respond to the environmental stressors in space. We used experimental evolution for 100-days in high aspect ratio vessels followed by whole genome resequencing to evaluate this adaptive response. Our data shows that planktonic S. mutans did evolve variants in three genes (pknB, SMU_399 and SMU_1307c) that can be uniquely attributed to simulated microgravity populations. In addition, collection of data at multiple time points showed mutations in three additional genes (SMU_399, ptsH and rex) that were detected earlier in simulated microgravity populations than in the normal gravity controls, many of which are consistent with other studies. Comparison of virulence-related phenotypes between biological replicates from simulated microgravity and control orientation cultures generally showed few changes in antibiotic susceptibility, while acid tolerance and adhesion varied significantly between biological replicates and decreased as compared to the ancestral populations. Most importantly, our data shows the importance of a parallel normal gravity control, sequencing at multiple time points and the use of biological replicates for appropriate analysis of adaptation in simulated microgravity.

Research paper thumbnail of 8. Evolutionary Versus Racial Medicine Why It Matters

Research paper thumbnail of Three domains of life—structure and function (Bacteria, Archaea, Eucarya)

Research paper thumbnail of Does it really matter if you win or lose the genetic lottery?

Research paper thumbnail of Racial Biology and Medical Misconceptions

The New England Journal of Medicine, Feb 10, 2022

Research paper thumbnail of Biological Theories of Race beyond the Millennium

Oxford University Press eBooks, May 24, 2018

This chapter provides historical contextualization of the crisis faced by the social construction... more This chapter provides historical contextualization of the crisis faced by the social construction approach of race. It reveals that anatomically modern humans are a young species that spent the majority of their existence living in a narrow range of eastern Africa. Indeed the exit of our species has been pushed forward in time from previous estimates. Evolutionary forces of natural selection and genetic drift have differentiated human populations, but this differentiation has been small. Most of the signal of human differentiation occurs in noncoding loci that do not face the force of purifying selection. Within the coding loci, some adaptation to local conditions has occurred. This adaptation does not allow the unambiguous classification of human populations into biological races.

Research paper thumbnail of Structural Racism and Science

Routledge eBooks, Oct 19, 2022

Research paper thumbnail of Genetics and American Science

Routledge eBooks, Oct 19, 2022

Research paper thumbnail of Pharmaceuticals/biotechnology—engineered proteins, vaccines, DNA vaccines

Research paper thumbnail of Characteristics of nanomaterials: composition, coating, size, shape, surface properties, physical properties (inorganic, polymeric)

Research paper thumbnail of Why We Must Teach Our Students about Race

The American Biology Teacher

Research paper thumbnail of People, We Have a Problem: Comment

Anesthesiology, Aug 8, 2023

Research paper thumbnail of Bacteriophages and viruses (not alive, but important)

Research paper thumbnail of What Darwin never saw: how things differ between the microbial and macroscopic world. (Horizontal gene transfer, co-selection, persister cells)

Research paper thumbnail of Fruit Fly Aging and Mortality

Science, Jun 11, 1993

Published by the American Association for the Advancement of Science (AAAS), Science serves its r... more Published by the American Association for the Advancement of Science (AAAS), Science serves its readers as a forum for the presentation and discussion of important issues related to the advancement of science, including the presentation of minority or conflicting points of view, rather than by publishing only material on which a consensus has been reached. Accordingly, all articles published in Science-including editorials, news and comment, and book reviews-are signed and reflect the individual views of the authors and not official points of view adopted by the AAAS or the institutions with which the authors are affiliated.

Research paper thumbnail of Co-adaptation of Streptococcus mutans to simulated microgravity and silver nitrate

Frontiers in Astronomy and Space Sciences, Jun 15, 2023

To sustain life on extended space missions, it is essential to maintain clean potable water. NASA... more To sustain life on extended space missions, it is essential to maintain clean potable water. NASA currently uses iodine as the primary biocide in the potable water dispenser on the International Space Station and has recently proposed a potential switch to silver-based antimicrobials. Streptococcus mutans is the primary etiological agent of dental caries, part of the normal oral flora, and would endure direct exposure to water from the potable water dispenser. In our previous work, we examined the 100-day adaptive response of Streptococcus mutans to simulated microgravity (sMG). Here, we examined the evolutionary co-adaptation of S. mutans under sMG and silver nitrate (AgNO3) to evaluate the consequences of using silver as a primary biocide in space and the impact on the evolution of microbes from the oral microbiome. To do this, we adapted four populations of S. mutans under sMG and co-adapted four populations in simulated microgravity and silver nitrate using high-aspect ratio vessels for 100 days. Genomic analysis at multiple time points showed that S. mutans in sMG evolved variants consistent with our previous findings (SMU_1307c and SMU_399) while also acquiring novel mutations in the glutathione reductase gorA. The co-adapted populations showed mutations specific for the environment in ciaH/R, PBP1a, trkA, and trkB. We also assessed virulence phenotypes, and while simulated microgravity increased antibiotic susceptibility, sucrose-dependent adhesion, and, in some populations, acid tolerance, co-adaptation to silver nitrate reversed these effects. Overall, these data show that the use of silver as a biocide in simulated microgravity can evolve strains with novel genotypic and phenotypic traits that could alter virulence.

Research paper thumbnail of Inequality in science and the case for a new agenda

Proceedings of the National Academy of Sciences of the United States of America, Feb 24, 2022

The history of the scientific enterprise demonstrates that it has supported gender, identity, and... more The history of the scientific enterprise demonstrates that it has supported gender, identity, and racial inequity. Further, its institutions have allowed discrimination, harassment, and personal harm of racialized persons and women. This has resulted in a suboptimal and demographically narrow research and innovation system, a concomitant limited lens on research agendas, and less effective knowledge translation between science and society. We argue that, to reverse this situation, the scientific community must reexamine its values and then collectively embark upon a moonshot-level new agenda for equity. This new agenda should be based upon the foundational value that scientific research and technological innovation should be prefaced upon progress toward a better world for all of society and that the process of how we conduct research is just as important as the results of research. Such an agenda will attract individuals who have been historically excluded from participation in science, but we will need to engage in substantial work to overcome the longstanding obstacles to their full participation. We highlight the need to implement this new agenda via a coordinated systems approach, recognizing the mutually reinforcing feedback dynamics among all science system components and aligning our equity efforts across them.

Research paper thumbnail of Experimental evolution of gallium resistance in Escherichia coli

Evolution, medicine & public health, 2019

Background and Objectives: Metallic antimicrobial materials are of growing interest due to their ... more Background and Objectives: Metallic antimicrobial materials are of growing interest due to their potential to control pathogenic and multidrug-resistant bacteria. Yet we do not know if utilizing these materials can lead to genetic adaptations that produce even more dangerous bacterial varieties. Methodology: Here we utilize experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to, the iron analog, gallium nitrate (Ga(NO 3) 3). Whole genome sequencing was utilized to determine genomic changes associated with gallium resistance. Computational modeling was utilized to propose potential molecular mechanisms of resistance. Results: By day 10 of evolution, increased gallium resistance was evident in populations cultured in medium containing a sublethal concentration of gallium. Furthermore, these populations showed increased resistance to ionic silver and iron (III), but not iron (II) and no increase in traditional antibiotic resistance compared with controls and the ancestral strain. In contrast, the control populations showed increased resistance to rifampicin relative to the gallium-resistant and ancestral population. Genomic analysis identified hard selective sweeps of mutations in several genes in the gallium (III)-resistant lines including: fecA (iron citrate outer membrane transporter), insl1 (IS30 tranposase) one intergenic mutations arsC !/! yhiS; (arsenate reductase/pseudogene) and in one pseudogene yedN ; (iapH/yopM family). Two additional significant intergenic polymorphisms were found at frequencies > 0.500 in fepD /! entS (iron-enterobactin transporter subunit/enterobactin exporter, iron-regulated) and yfgF /! yfgG (cyclic-di-GMP phosphodiesterase, anaerobic/uncharacterized protein). The control populations displayed mutations in the rpoB gene, a gene associated with rifampicin resistance. Conclusions: This study corroborates recent results observed in experiments utilizing pathogenic Pseudomonas strains that also showed that Gram-negative bacteria can rapidly evolve resistance to original research article

Research paper thumbnail of Genomic evolution of antibiotic resistance is contingent on genetic background following a long-term experiment with <i>Escherichia coli</i>

Proceedings of the National Academy of Sciences of the United States of America, Jan 13, 2021

Antibiotic resistance is a growing health concern. Efforts to control resistance would benefit fr... more Antibiotic resistance is a growing health concern. Efforts to control resistance would benefit from an improved ability to forecast when and how it will evolve. Epistatic interactions between mutations can promote divergent evolutionary trajectories, which complicates our ability to predict evolution. We recently showed that differences between genetic backgrounds can lead to idiosyncratic responses in the evolvability of phenotypic resistance, even among closely related Escherichia coli strains. In this study, we examined whether a strain's genetic background also influences the genotypic evolution of resistance. Do lineages founded by different genotypes take parallel or divergent mutational paths to achieve their evolved resistance states? We addressed this question by sequencing the complete genomes of antibiotic-resistant clones that evolved from several different genetic starting points during our earlier experiments. We first validated our statistical approach by quantifying the specificity of genomic evolution with respect to antibiotic treatment. As expected, mutations in particular genes were strongly associated with each drug. Then, we determined that replicate lines evolved from the same founding genotypes had more parallel mutations at the gene level than lines evolved from different founding genotypes, although these effects were more subtle than those showing antibiotic specificity. Taken together with our previous work, we conclude that historical contingency can alter both genotypic and phenotypic pathways to antibiotic resistance.

Research paper thumbnail of Science, Empire, and Imperialism

Routledge eBooks, Oct 19, 2022

Research paper thumbnail of Adaptation to simulated microgravity in Streptococcus mutans

NPJ microgravity, Jun 2, 2022

Long-term space missions have shown an increased incidence of oral disease in astronauts' and as ... more Long-term space missions have shown an increased incidence of oral disease in astronauts' and as a result, are one of the top conditions predicted to impact future missions. Here we set out to evaluate the adaptive response of Streptococcus mutans (etiological agent of dental caries) to simulated microgravity. This organism has been well studied on earth and treatment strategies are more predictable. Despite this, we are unsure how the bacterium will respond to the environmental stressors in space. We used experimental evolution for 100-days in high aspect ratio vessels followed by whole genome resequencing to evaluate this adaptive response. Our data shows that planktonic S. mutans did evolve variants in three genes (pknB, SMU_399 and SMU_1307c) that can be uniquely attributed to simulated microgravity populations. In addition, collection of data at multiple time points showed mutations in three additional genes (SMU_399, ptsH and rex) that were detected earlier in simulated microgravity populations than in the normal gravity controls, many of which are consistent with other studies. Comparison of virulence-related phenotypes between biological replicates from simulated microgravity and control orientation cultures generally showed few changes in antibiotic susceptibility, while acid tolerance and adhesion varied significantly between biological replicates and decreased as compared to the ancestral populations. Most importantly, our data shows the importance of a parallel normal gravity control, sequencing at multiple time points and the use of biological replicates for appropriate analysis of adaptation in simulated microgravity.

Research paper thumbnail of 8. Evolutionary Versus Racial Medicine Why It Matters

Research paper thumbnail of Three domains of life—structure and function (Bacteria, Archaea, Eucarya)

Research paper thumbnail of Does it really matter if you win or lose the genetic lottery?

Research paper thumbnail of Racial Biology and Medical Misconceptions

The New England Journal of Medicine, Feb 10, 2022

Research paper thumbnail of Biological Theories of Race beyond the Millennium

Oxford University Press eBooks, May 24, 2018

This chapter provides historical contextualization of the crisis faced by the social construction... more This chapter provides historical contextualization of the crisis faced by the social construction approach of race. It reveals that anatomically modern humans are a young species that spent the majority of their existence living in a narrow range of eastern Africa. Indeed the exit of our species has been pushed forward in time from previous estimates. Evolutionary forces of natural selection and genetic drift have differentiated human populations, but this differentiation has been small. Most of the signal of human differentiation occurs in noncoding loci that do not face the force of purifying selection. Within the coding loci, some adaptation to local conditions has occurred. This adaptation does not allow the unambiguous classification of human populations into biological races.

Research paper thumbnail of Structural Racism and Science

Routledge eBooks, Oct 19, 2022

Research paper thumbnail of Genetics and American Science

Routledge eBooks, Oct 19, 2022

Research paper thumbnail of Pharmaceuticals/biotechnology—engineered proteins, vaccines, DNA vaccines

Research paper thumbnail of Characteristics of nanomaterials: composition, coating, size, shape, surface properties, physical properties (inorganic, polymeric)