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Project Title:  Genomic & Phenotypic Changes in Yeast Related to Selective Growth Pressures Unique to Microgravity Reduce
Fiscal Year: FY 2008 
Division: Physical Sciences 
Research Discipline/Element:
Physical Sciences: BIOTECHNOLOGY--Biotechnology  		Start Date: 12/01/2003  
End Date: 11/30/2007  
Task Last Updated: 07/02/2008 		 Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Hyman, Linda  Ph.D. / Boston University 
Address:  Department of Microbiology 
L317 
Boston , MA 02215 		 Email: lhyman@bu.edu 
Phone: 617 638 5138  
Congressional District: 8 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Boston University 
Joint Agency:  
Comments: NOTE: PI formerly at Montana State University; move to Boston University effective 7/1/2009 (6/29/09) 
Co-Investigator(s)
Affiliation: 
Nielsen-Preiss, Sheila  Montana State University 
Key Personnel Changes / Previous PI: 0
Project Information: Grant/Contract No. NNJ04HC74G 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Unique ID: 4162  		Solicitation / Funding Source: 2001 Physical Sciences 01-OBPR-08 
Grant/Contract No.: NNJ04HC74G 
Project Type: Ground 
Flight Program:   		No. of Post Docs: 1 
No. of PhD Candidates: 0 
No. of Master's Candidates: 0 
No. of Bachelor's Candidates: 3  		No. of PhD Degrees: 0 
No. of Master's Degrees: 0 
No. of Bachelor's Degrees: 0 
Program--Element: BIOTECHNOLOGY--Biotechnology 
Flight Assignment/Project Notes: NOTE: Funding reinstated to 11/30/2007, per J. Cohen (HQ, 8/2006)

Task Description: Our experiments focus on understanding how cells adapt to the unique conditions of microgravity in the space, using the model eukaryotic organism, Saccharomyces cerevisiae. We will utilize two types of yeast microarray analysis, RNA ‘expression’ profiling and ‘fitness’ profiling. One set of experiments is designed to establish gene expression in the rotary suspension culture system that models microgravity conditions similar to the space environment. Once we identify genes regulating growth under selective pressure, we will confirm and extend our experiments, conducting parallel experiments with the yeast deletion series. Utilization of the yeast deletion series allows a genomic approach to phenotypic analysis of every strain representing the ~6000 genes in the yeast genome. Our hypothesis is that yeast cells will undergo a selective response to microgravity and that phenotypic responses are controlled by changes in gene expression of specific target genes. We expect this novel approach of comparing expression and fitness profiling datasets to confirm some genes revealed by RNA expression analysis and also to reveal new genes required for growth that are not necessarily regulated transcriptionally.

Task Objectives 1. Identify yeast gene expression under selective pressure of low shear modeled microgravity in the HARV (completed, Years 1 and 2). 2. Confirm and extend preliminary work that identified specific promoter motifs that respond to changes in gene expression during growth in the HARV (ongoing). 3. Utilize a powerful genome-wide approach for analysis of highly specific alterations in eukaryotic cells attributable to microgravity (to be undertaken in Year 3). 4. Gain an understanding of biological mechanisms that may increase the health risks to humans during long-duration space flight (additional focus that addresses new critical path roadmap issues).

Our research objectives can provide answers to questions addressing risks for human space flight. First, we can address whether microgravity exerts any selective pressures upon yeast cells. Second, we can answer whether space flight alters microbial growth rates and/or cell characteristics. Third, our research will provide insights into the molecular and genetic mechanisms that are affected by space flight related environments.

Research Impact/Earth Benefits: Regulatory mechanisms are largely conserved between yeast and mammalian cells. The ease of genetic manipulation, genome sequence information, and readily available commercial reagents in yeast facilitates the analysis of phenotypic and genotypic changes under selective growth conditions. Our expectation is that any biological effects observed in yeast cells in space will be similar to effects occurring in eukaryotic, mammalian cells. We hope genetic analysis will give clues to signaling mechanisms responsible for changes in gene expression. Any biological effects we identify may have direct implications for human space flight and long-term space missions. We hope our studies will establish methods for fitness profiling for other earth-based studies of stress responses. Furthermore, we believe that our phenotypic analysis results in Year 2 provide a platform for understanding developmental processes of higher eukaryotes that are known to employ spatially ordered and/or asymmetric cell division patterns. In addition, we have identified key regulatory genes responsible for biofim development in yeast that are differentially expressed in simulated microgravity. Further exploration of these results and uncovering the genetic and physiological factors affecting processes, will have important fundamental and medical implications.

Task Progress & Bibliography Information FY2008 
Task Progress: The final report for our grant describes the results that appear in four published manuscripts. The first discusses the effect of simulated microgravity in the yeast Saccahryomes cerevisiae demonstrating a clear phenotypic response to these growth conditions. In addition we show the molecular changes that accompany the morphological response we observe. The second presents the genomic response to growth in simulated microgravity which confims and extends out earlier observation. In a third and most recent paper we show that the response observed in Saccharomyces is conserved in the pathogenetic yeast, Candida albicans, which has significant implications for space flight. Future experiments will focus on this observation, particualry as it relates to increased pathogenesis and biofilm formation as the microorganism is exposed to microgravity conditions.

Bibliography: Description: (Last Updated: 07/02/2008) 

Show Cumulative Bibliography
 
Articles in Peer-reviewed Journals Altenburg SD, Nielsen-Preiss SM, Hyman LE. "Increased filamentous growth of Candida albicans in simulated microgravity." Genomics Proteomics Bioinformatics. 2008 Feb;6(1):42-50. PMID: 18558384 , Feb-2008
Articles in Peer-reviewed Journals Purevdorj-Gage B, Orr ME, Stoodley P, Sheehan KB, Hyman LE. "The role of FLO11 in Saccharomyces cerevisiae biofilm development in a laboratory based flow-cell system." FEMS Yeast Res. 2007 May;7(3):372-9. Epub 2007 Jan 19. PMID: 17233763 , May-2007
Articles in Peer-reviewed Journals Sheehan KB, McInnerney K, Purevdorj-Gage B, Altenburg SD, Hyman LE. "Yeast genomic expression patterns in response to low-shear modeled microgravity." BMC Genomics. 2007 Jan 3;8:3. PMID: 17201921 , Jan-2007
Articles in Peer-reviewed Journals Purevdorj-Gage B, Sheehan KB, Hyman LE. "Effects of low-shear modeled microgravity on cell function, gene expression, and phenotype in Saccharomyces cerevisiae." Appl Environ Microbiol. 2006 Jul;72(7):4569-75. PMID: 16820445 , Jul-2006
Back to Search Results    
Project Title:  Genomic & Phenotypic Changes in Yeast Related to Selective Growth Pressures Unique to Microgravity Reduce
Fiscal Year: FY 2006 
Division: Physical Sciences 
Research Discipline/Element:
Physical Sciences: BIOTECHNOLOGY--Biotechnology  		Start Date: 12/01/2003  
End Date: 11/30/2007  
Task Last Updated: 10/03/2005 		 Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Hyman, Linda  Ph.D. / Boston University 
Address:  Department of Microbiology 
L317 
Boston , MA 02215 		 Email: lhyman@bu.edu 
Phone: 617 638 5138  
Congressional District: 8 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Boston University 
Joint Agency:  
Comments: NOTE: PI formerly at Montana State University; move to Boston University effective 7/1/2009 (6/29/09) 
Key Personnel Changes / Previous PI: 0
Project Information: Grant/Contract No. NNJ04HC74G 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Unique ID: 4162  		Solicitation / Funding Source: 2001 Physical Sciences 01-OBPR-08 
Grant/Contract No.: NNJ04HC74G 
Project Type: Ground 
Flight Program:   		No. of Post Docs: 1 
No. of PhD Candidates: 0 
No. of Master's Candidates: 0 
No. of Bachelor's Candidates: 2  		No. of PhD Degrees: 0 
No. of Master's Degrees: 0 
No. of Bachelor's Degrees: 0 
Program--Element: BIOTECHNOLOGY--Biotechnology 
Flight Assignment/Project Notes: NOTE: Funding reinstated to 11/30/2007, per J. Cohen (HQ, 8/2006)

Task Description: Our experiments focus on understanding how cells adapt to the unique conditions of microgravity in the space, using the model eukaryotic organism, Saccharomyces cerevisiae. We will utilize two types of yeast microarray analysis, RNA ‘expression’ profiling and ‘fitness’ profiling. One set of experiments is designed to establish gene expression in the rotary suspension culture system that models microgravity conditions similar to the space environment. Once we identify genes regulating growth under selective pressure, we will confirm and extend our experiments, conducting parallel experiments with the yeast deletion series. Utilization of the yeast deletion series allows a genomic approach to phenotypic analysis of every strain representing the ~6000 genes in the yeast genome. Our hypothesis is that yeast cells will undergo a selective response to microgravity and that phenotypic responses are controlled by changes in gene expression of specific target genes. We expect this novel approach of comparing expression and fitness profiling datasets to confirm some genes revealed by RNA expression analysis and also to reveal new genes required for growth that are not necessarily regulated transcriptionally. Task Objectives 1. Identify yeast gene expression under selective pressure of low shear modeled microgravity in the HARV (completed, Years 1 and 2). 2. Confirm and extend preliminary work that identified specific promoter motifs that respond to changes in gene expression during growth in the HARV (ongoing). 3. Utilize a powerful genome-wide approach for analysis of highly specific alterations in eukaryotic cells attributable to microgravity (to be undertaken in Year 3). 4. Gain an understanding of biological mechanisms that may increase the health risks to humans during long-duration space flight (additional focus that addresses new critical path roadmap issues). Our research objectives can provide answers to questions addressing risks for human space flight. First, we can address whether microgravity exerts any selective pressures upon yeast cells. Second, we can answer whether space flight alters microbial growth rates and/or cell characteristics. Third, our research will provide insights into the molecular and genetic mechanisms that are affected by space flight related environments.

Research Impact/Earth Benefits: Regulatory mechanisms are largely conserved between yeast and mammalian cells. The ease of genetic manipulation, genome sequence information, and readily available commercial reagents in yeast facilitates the analysis of phenotypic and genotypic changes under selective growth conditions. Our expectation is that any biological effects observed in yeast cells in space will be similar to effects occurring in eukaryotic, mammalian cells. We hope genetic analysis will give clues to signaling mechanisms responsible for changes in gene expression. Any biological effects we identify may have direct implications for human space flight and long-term space missions. We hope our studies will establish methods for fitness profiling for other earth-based studies of stress responses. Furthermore, we believe that our phenotypic analysis results in Year 2 provide a platform for understanding developmental processes of higher eukaryotes that are known to employ spatially ordered and/or asymmetric cell division patterns. In addition, we have identified key regulatory genes responsible for biofim development in yeast that are differentially expressed in simulated microgravity. Further exploration of these results and uncovering the genetic and physiological factors affecting processes, will have important fundamental and medical implications.

Task Progress & Bibliography Information FY2006 
Task Progress: We have made significant progress towards our research objectives outlined as follows. 1. Cell Morphology. We have discovered that during growth in simulated microgravity, S. cerevisiae displays aberrations in normal cell division patterns. 2. Biofilms. We have identified key regulatory genes responsible for biofilm development in yeast that are differentially expressed in simulated microgravity. 3. Microarray Analysis. After expression profiling experiments, we found significant differences attributable to the stress of simulated microgravity.

Bibliography: Description: (Last Updated: 07/02/2008) 

Show Cumulative Bibliography
 
 None in FY 2006
Back to Search Results    
Project Title:  Genomic & Phenotypic Changes in Yeast Related to Selective Growth Pressures Unique to Microgravity Reduce
Fiscal Year: FY 2005 
Division: Physical Sciences 
Research Discipline/Element:
Physical Sciences: BIOTECHNOLOGY--Biotechnology  		Start Date: 12/01/2003  
End Date: 09/30/2006  
Task Last Updated: 12/02/2004 		 Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Hyman, Linda  Ph.D. / Boston University 
Address:  Department of Microbiology 
L317 
Boston , MA 02215 		 Email: lhyman@bu.edu 
Phone: 617 638 5138  
Congressional District: 8 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Boston University 
Joint Agency:  
Comments: NOTE: PI formerly at Montana State University; move to Boston University effective 7/1/2009 (6/29/09) 
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor: Kirby, Mary  
Center Contact:  
mary.f.kirby@nasa.gov 
Unique ID: 4162  		Solicitation / Funding Source: 01-OBPR-08-B 
Project Type: Ground 
Flight Program:   		No. of Post Docs: 0 
No. of PhD Candidates: 0 
No. of Master's Candidates: 0 
No. of Bachelor's Candidates: 3  		No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Program--Element: BIOTECHNOLOGY--Biotechnology 
Task Description: Our experiments focus on understanding how cells adapt to the conditions of microgravity in the space environment, using the model eukaryotic organism, Saccharomyces cerevisiae. We will utilize two types of yeast deletion strains. One set of experiments is designed to establish gene expression in the rotary suspension culture system. Once we identify genes regulating growth under selective pressure, we will confirm and extend our experiments in a true microgravity environment, utilizing the yeast deletion series, a mixture of 6000 molecularly engineered isogenic yeast strains that differ only in a single gene locus and represent every gene in the yeast genome. Each gene is identified by a unique ‘bar code’. The deletion series will be grown under selective pressure, DNA extracted, and the bar codes amplified by PCR. The resulting PCR product will be annealed to a gene microarray chip comprised of spots with complimentary sequences for each bar code. This allows a genomic approach to phenotypic analysis of every strain in the yeast deletion series. Our hypothesis is that yeast cells will undergo a selective response to microgravity and that phenotypic responses are controlled by changes in gene expression of specific target genes.

Research Impact/Earth Benefits: Regulatory mechanisms are largely conserved between yeast and mammalian cells. The ease of genetic manipulation, genome sequence information, and readily available commercial reagents in yeast facilitates the analysis of phenotypic and genotypic changes under selective growth conditions. Our expectation is that any biological effects observed in yeast cells in space will be similar to effects occurring in eukaryotic, mammalian cells. We hope genetic analysis will give clues to signaling mechanisms responsible for changes in gene expression. Any biological effects we identify may have direct implications for human space flight and long-term space missions. We hope our studies will establish methods for fitness profiling for other earth-based studies of stress responses.

Task Progress & Bibliography Information FY2005 
Task Progress: We mimicked some aspects of microgravity in our ground-based, preliminary studies in the laboratory, by using a rotary suspension culture system (Synthecon, RCCS-4) equipped with a High-Aspect-Ratio-Vessel (HARV). The HARV is a culture vessel that mimics microgravity by providing for the cells: a) randomized orientation to the gravity vector and b) falling at terminal velocity. The HARV also allows ample gas exchange for yeast growth via a permeable membrane. Our previous research showed changes in gene expression during rotating wall vessel suspension culture. A significant number of genes were found to be up- or down- regulated by at least two-fold as a result of rotational growth (Johanson, et al., 2002, J. Appl. Physiol. 93:2171-2180). In order to assure that any gene expression changes we might identify when using the RCCS-4 rotary cell culture system equipped with HARVs are due to effects of the microgravity environment and not due to metabolic factors, we determined the major growth phases and diauxic shift for BY4741. We also determined inoculum volumes for the HARVs, extraction methods for total RNA from the cultured cells, and techniques for cDNA preparation using RT-PCR.

Bibliography: Description: (Last Updated: 07/02/2008) 

Show Cumulative Bibliography
 
 None in FY 2005
Back to Search Results    
Project Title:  Genomic & Phenotypic Changes in Yeast Related to Selective Growth Pressures Unique to Microgravity Reduce
Fiscal Year: FY 2004 
Division: Physical Sciences 
Research Discipline/Element:
Physical Sciences: BIOTECHNOLOGY--Biotechnology  		Start Date: 12/01/2003  
End Date: 11/30/2007  
Task Last Updated: 03/28/2006 		 Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Hyman, Linda  Ph.D. / Boston University 
Address:  Department of Microbiology 
L317 
Boston , MA 02215 		 Email: lhyman@bu.edu 
Phone: 617 638 5138  
Congressional District: 8 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Boston University 
Joint Agency:  
Comments: NOTE: PI formerly at Montana State University; move to Boston University effective 7/1/2009 (6/29/09) 
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor: Kirby, Mary  
Center Contact:  
mary.f.kirby@nasa.gov 
Unique ID: 4162  		Solicitation / Funding Source: 2001 Physical Sciences 01-OBPR-08 
Project Type: Ground 
Flight Program:   		No. of Post Docs: 0 
No. of PhD Candidates: 0 
No. of Master's Candidates: 0 
No. of Bachelor's Candidates: 3  		No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Program--Element: BIOTECHNOLOGY--Biotechnology 
Task Description: Our experiments focus on understanding how cells adapt to the conditions of microgravity in the space environment, using the model eukaryotic organism, Saccharomyces cerevisiae. We will utilize two types of yeast deletion strains. One set of experiments is designed to establish gene expression in the rotary suspension culture system. Once we identify genes regulating growth under selective pressure, we will confirm and extend our experiments in a true microgravity environment, utilizing the yeast deletion series, a mixture of 6000 molecularly engineered isogenic yeast strains that differ only in a single gene locus and represent every gene in the yeast genome. Each gene is identified by a unique ‘bar code’. The deletion series will be grown under selective pressure, DNA extracted, and the bar codes amplified by PCR. The resulting PCR product will be annealed to a gene microarray chip comprised of spots with complimentary sequences for each bar code. This allows a genomic approach to phenotypic analysis of every strain in the yeast deletion series. Our hypothesis is that yeast cells will undergo a selective response to microgravity and that phenotypic responses are controlled by changes in gene expression of specific target genes.

Research Impact/Earth Benefits: Regulatory mechanisms are largely conserved between yeast and mammalian cells. The ease of genetic manipulation, genome sequence information, and readily available commercial reagents in yeast facilitates the analysis of phenotypic and genotypic changes under selective growth conditions. Our expectation is that any biological effects observed in yeast cells in space will be similar to effects occurring in eukaryotic, mammalian cells. We hope genetic analysis will give clues to signaling mechanisms responsible for changes in gene expression. Any biological effects we identify may have direct implications for human space flight and long-term space missions. We hope our studies will establish methods for fitness profiling for other earth-based studies of stress responses.

Task Progress & Bibliography Information FY2004 
Task Progress: New project for FY2004; no progress report this period.

Bibliography: Description: (Last Updated: 07/02/2008) 

Show Cumulative Bibliography
 
 None in FY 2004
Back to Search Results