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MANAGEMENT PLAN FOR NATIONAL SCIENCE & TECHNOLOGY CENTER FOR FUNGAL GENOMICS

 
 

The National Science & Technology Center for Fungal Genomics includes the partnership of 5 US universities, University of Georgia (UGA), University of Cincinnati (UC), University of New Mexico (UNM), Dartmouth University, and Texas A&M (A&M) University with 7 German universities, Heinrich-Heine-Universitaet Dusseldorf, Ludwig-Maximilians-Universitaet Munchen, Albert-Ludwigs-Universitaet Freiburg, Eberhard-Karls-Universitaet Tuebingen, Universitaet Bremen, and Ruhr Universitaet Bochum as well as the Institut de Pasteur - Lille in France.

There is an External Advisory Board to provide advice, review progress, provide community input, and determine how the resource is to be used ethically by the Scientific Community, Science and Mathematics Education Community, and industry to promote: research in Fungal Genomics, the integration of genomics into science and mathematics education, the promotion of full human diversity in science and education, and genome technology transfer. The members of the external advisory board are Drs. Prentice Baptiste/New Mexico State University/Science Education, Mary E. Brawner/Smith Kline Beecham/Technology Transfer, Angelo Collins/Vanderbilt University/Science Education, Lee Hood/University of Washington/Genomics, Patrick Jordan/SREC-USDA/technology transfer, Richard Karp/University of Washington/Computational Biology, David Magnus/University of Pennsylvania/Bioethics, Robert L. Metzenberg/Stanford University/Fungal Genetics and Biochemistry, Maynard Olson/University of Washington/Genomics, Bruce Roe/University of Oklahoma/Genomics and Michael Waterman/University of Southern California/Computational Biology and provide representatives from academia, industry, and education. The director of the facility is Dr. Jonathan Arnold/UGA and the co-director, Dr. Mary Anne Nelson/UNM. Both provide interdisciplinary expertise in genomics and have extensive science administration experience.

There are 11 core groups in FGR: (i) Bioethics; (ii) instrumentation; (iii) genomic sequencing; (iv) physical mapping; (v) functional genomics; (vi) evolutionary genomics; (vii) informatics; (viii) databases; (ix) education; (x) technology transfer; (xi) administration.

a. External Advisory Board. The role of the advisory board is to:

1. provide advice;

2. provide community input;

3. ensure equitable use of the resource by the Fungal Genetics Community;

4..provide independent outside review of the performance of the STC.

The external advisory board represents a mix of scientists and educators capable of evaluating the full range of STC activities.

Action Committee: The action committee is the governing body for the STC with one voting member per institution (University of Georgia, Dartmouth University, University of Cincinnati, University of New Mexico, and Texas A & M University). All actions are taken on motions that pass by 3 out of 5 votes. The director is the PI of the grant proposal, and the Co-director is a Co-PI at a different institution elected by the Action Committee. Members are: R. Aramayo/A&M, J. Arnold/UGA, J. Dunlap/Dartmouth, D. Natvig/UNM, M. Nelson/UNM, and M. Cushion/UC.

b. Co-Directors. The role of the director (PI) and co-director is to:

1. provide leadership in how the STC is to be used to facilitate studies on fungal genomics. In particular, they will oversee:

2. sequencing the 42.9 Mb Neurospora crassa and 7.7 Mb Pneumocystis carinii genomes.

3. developing new experimental and mathematical strategies and instrumentation for understanding the function and evolution of many genes at once.

4. integrate genomics research into secondary, undergraduate, and graduate education education with research experiences, summer institutes, promoting science as a way of knowing, teacher enhancement, and industrial/national laboratory internships.

5. Develop a technology transfer mechanisms linked to the bioethical consequences of these products to companies that can exploit genomics in developing new products.

6. implement the advice of the External Advisory Board;

Drs. M.A. Nelson/UNM and J. Arnold/UGA provide complementary research expertise in directing the STC. Dr. Nelson provides critical expertise in science education and large scale genomic sequencing, and Dr. Arnold provides critical expertise in fungal genomics and computational biology. Both have extensive administrative experience. Dr. Arnold was the creator and director of the NSF-funded BioScience Computational Resource (BSCR) for three years. This facility grew to serve over 75 laboratories and 350 scientists by the end of his term. BSCR was so successful that Dr. Arnold ran it as a self-supporting resource. University Computing and Networking Services continues to operate this highly successful resource (see Facilities).

The various cores contain the core leaders as well as students and postdoctoral fellows associated with professors in each core.

c. Bioethics Core. The role of the Bioethics Core is to:

1. decide on the ethical consequences of fungal genomics;

2. determine policies on the deployment of new genome technologies and knowledge infranstructure;

3. assess public awareness of fungal genomics;

4. educate the public about the social and political implications of genomics.

Dr. Celeste Condit/UGA is associate director of the the Bioethics Core and has a research specialty in the public policy of genomics and is currently funded by NIH in this area. She is developing a core curriculum in genomics for undergraduates that will also be used in our summer institute for precollege teachers and high school students. Her role on the project is to supervise the bioethical and public policy activities of the STC. They have a monthly seminar for this core activity.

Members of the Bioethics Core include V. Davion/UGA, R. Hodson/UGA, S. Kleiner/UGA, V. Nazarea/UGA, C. Wolf/UGA.

d. Instrumentation Core. The role of the Instrumentation Core is to:

1. design and supervise the building of the robotics systems for fungal genomics;

2. periodically test robotics systems for proper performance;

3. redesign the robotics system with changes to improved experimental protocols;

4. redesign robotics systems in response to suggestions from other cores.

5. troubleshoot problems with the operation of robotics systems;

6. connect the Fungal Genome Database (FGDB) to robotics systems.

Dr. Charles Keith/UGA is associate director of the Instrumentation Core and has a research specialty in biological instrumentation. Dr. Keith has extensive adminstrative experience and was in charge of the Multi-User Biological Instrumentation Program at NSF for one year and is also graduate coordinator of the Cellular Biology Department. His role on the project is the design, testing, adaptation, expansion, and automated implementation of genomics protocols. He supervises the creation and testing of a robotics system for physical mapping, called I.S.A.A.C. (Intelligient System forAutomated Assembly of Chromosomes). As experimental protocols evolve, he will be involved in the redesign and evolution of the genomics instrumentation.

The faculty in the instrumentation core include Dr.s Mark Farmer/UGA.

e. Mapping Core. The role of the Mapping Core is to:

1. implement automated physical mapping experiments;

2. operate associated Robotics systems like I.S.A.A.C;

3. provide feedback on the operation of the robots to the Instrumentation Core for improvements;

4. deposit mapping data with the Databases Core;

5. provide training and advice in the use of the robotics system by researchers.

Drs. J. Arnold/UGA, Mary Case/UGA, and Sarah Covert/UGA are associate directors of the Mapping Core, and Mr. James Griffith/UGA is laboratory coordinate of the mapping core. The activity of the Mapping Core is physical and genetic mapping in fungal genomics. Drs. Case and Covert are CO-PIs on an NSF-funded project to create a 29 kb resolution physical map of Neurospora crassa. Dr. Covert is PI on an NSF-funded project to create a 29 kb resolution physical maps of supernumerary chromosomes of Nectria haematococca. The former head of the mapping core, Dr. Prade, and Mr. Griffith have completed 99.1% of the physical map of the A. nidulans genome at 29 kb resolution (Prade et al., 1997). Mr. Griffith has been on the mapping project of A. nidulans for 9 years and carried out all the physical mapping experiments on A. nidulans. Drs. Case and Covert supervise the experimental uses of FGR, and Mr. Griffith operates the robotics instrumenation. They have a biweekly seminar for this core activity.

Members of the Mapping core include M. Sachs/Oregon Graduate Institute.

f. Sequencing Core. The role of the Sequencing Core is to:

1. implement the automated genomic sequencing experiments;

2. operate associated Robotics systems;

3. provide feedback on the operation of the robots to the Instrumentation Core for improvements;

4. deposit sequencing data with the Databases Core;

5. provide training and advice in the use of the robotics system by researchers.

Drs. Nelson/UNM, D. Natvig/UNM, and U. Schulte/Heinrich-Heine-Universitat Dusseldorf are associate directors of the Sequencing Core, and H. Kelkar/UGA and Mr. David Brown/UGA constitute the Sequencing Core. Dr. D. Brown/UGA is laboratory coordinator for this core. Drs. Natvig and Nelson has recently completed the sequencing of 3000 cDNAs of Neurospora crassa (Nelson et al., 1997). Activities include cDNA sequencing and genomic sequencing. Dr. Schulte is funded for genomic sequencing of N. crassa chromosomes II and V in Germany. Dr. Kelkar is a postdoctoral fellow familiar with large scale sequencing and fungal genomics. Mr. Brown is a senior laboratory coordinator with extensive academic and industrial experience in molecular genetics. Drs. Nelson, Natvig, and Schulte supervise the experimental uses of STC, and Mr. Brown operates the robotics instrumentation.

Faculty members in the sequencing core include N. Keller/A&M, W.-H. Kunau/Ruhr Universitaet Bochum, J. Maier/Eberhard-Karls-Universitaet Tuebingen, H. Ninnemann and, W. Neupert/Ludwig-Maximilians-Universitaet Muenchen, L. Rensing/Universitaet Bremen, M. Schliwa/Ludwig-Maximilians-Universitaet Munchen, M. Tropschug/Albert-Ludwigs-Universitaet Munchen, M. Werner-Washburne/UNM, B. Whitman/UGA.

g. Functional Genomics Core. The role of the Functional Genomics Core is to:

1. implement the automated functional genomics experiments;

2. operate associated Robotics systems;

3. provide feedback on the operation of the robots to the Instrumentation Core for improvements;

4. deposit sequencing data with the Databases Core;

5. provide training and advice in the use of the robotics system by researchers.

Drs. Aramayo/A&M, J. Dunlap/Dartmouth, and G. Smulian/UC and Mr. J. Griffith/UGA constitute the Functional Genomics Core. Drs. R. Aramayo/A&M, J. Dunlap/Dartmouth, and G. Smulian/UC are associate directors of the Functional Genomics Core. Dr. Aramayo is engaged in scanning for transvection events along N. crassa chromosomes. Dr. Dunlap is pursuing sequencing cDNAS for transcriptional profiling the clock genome of N. crassa. Dr. G. Smulian is developing new vectors for creating knockout libraries in Pneumocystis carinii. Mr. Griffith is the most senior research coordinator in fungal genomics (Prade et al., 1997) with 9 years of experience in fungal genomics. Mr. Griffith will operate the robotics instrumenation for functional genomics.

Faculty members in the functional genomics core include D. Bell-Pedersen/A&M, J. Dean/UGA, D. Ebbole/A&M, C. Glover/UGA, J.C. Hu/A&M, J. Loros/Dartmouth, M. McEachern, T. Thomas/A&M, N. Van Alfen/A&M, R. Miller/UNM, M. Momany/UGA.

h. Evolutionary Genomics Core. The role of this core is to:

1. implement studies in fungal evolutionary genomics;

2. operate associated Robotics systems;

3. provide feedback on the operation of the robots to the Instrumentation Core for improvements;

4. deposit evolutionary data with the Databases Core;

5. provide training and advice in the use of the robotics system by researchers.

Drs. Stringer/UC and M. Cushion/UC are associate directors the Evolutionary Genomics Core. Dr. Cushion is the chairman of the Pneumocystis carinii Genome Project Initiative (PCGPI) and is engaged with Dr. Stringer in understanding an unusual site-specific genome rearrangment process at the ends of P. carinii chromosomes.

Members of the evolutionary genomics core include R. Hanlin/UGA, J. McDonald/UGA.

i. Informatics Core. The role of the Informatics Core is to:

1. develop statistical and computational methods for fungal genomics;

2. monitor the quality of genomics data generated by other Mapping, Sequencing, Functional Genomics, and Evolutionary Genomics coresand provide feedback on the map quality to these Cores and Databases Core;

3. train researchers in the use of FGR informatics methods.

Our group has been a leader in developing new statistical and computational methods in physical mapping. Drs. Suchi Bhandarkar/UGA and John Kececioglu/UGA, associate and assistant professors of computer science, respectively, are associate directors of the Informatics Core. They provide leadership to a group of students and postdoctoral fellows in the development of new computational and statistical tools for physical mapping. Dr. Bhandarkar is funded by the USDA Plant Genome Panel to create parallel algorithms for assembling physical maps. Dr. Kececioglu is funded by an NSF Career Development Award for DNA sequence assembly, sequence alignment, and other problems in computational biology. They have a weekly seminar for this core activity. Dr. A.J. Cuticchia/UGA, who was in this group, developed the first general purpose physical mapping method (Cuticchia et al., 1992a, 1993b), which we have distributed to several hundred laboratories. Xiong/UGA et al. (1996) were the first to provide a statistical justification for a physical mapping method. Dr. Xiong/UGA showed that as the number of probes is made very large, putting clones in order by their position along the chromosome by minimizing total linking distance almost always produces the correct order. Professor Wang/UGA recently provided the first statistical assessment of the reliability of a physical map by bootstrap resampling (Wang et al., 1994a, 1994b) as well as new fast physical mapping algorithms for PCs and Macintoshes.

Dr. Bhandarkar/UGA is developing new parallel algorithms for physical mapping (Bhandarkar and Arnold, 1994). Dr. Kececioglu/UGA developed the sequence assembly software now shipped commercially with the ABI sequenator. In addition, Dr. Kececioglu is actively pursuing a research program in the theoretical comparative mapping of fungal genomes (Kececioglu and Sankoff, 1994; Kececioglu and Ravi, 1995).

Faculty in in the Informatics core include Drs. E.R. Canfield/UGA, H. Chen/UGA, T. Taha/UGA, A. Wagner/UNM.

j. Databases Core: The role of the Databases Core is to:

1. further develop the Fungal Genome Database (FGDB);

2. store mapping information developed by the Mapping, Sequencing, Functional, and Evolutionary Genomics Cores;

3. provide retrieval and dissemination tools of mapping information for fungal genetics community;

4. provide training in the use of FGDB by the fungal genetics community;

5. incorporate new informatics methods developed by the Informatics Core into FGDB.

Dr. Krys Kochut/UGA, associate professor of computer science, is associate director of this Database Core. He has participated as a collaborator for five years with those in the STC, and he leads the group developing database tools for storing, retrieving, and disseminating fungal genomics data to the fungal genetics community. The core activity is to develop database tools for fungal genomics. This core includes other computer scientists, like Dr.s John Miller and Walter Potter. Dr. Kochut co-supervised the initial creation of a prototype genome database CMAP (Cuticchia et al., 1992). He is the developer of the Fungal Genome Database (FGDB). There are two publications to date describing FGDB (Miller et al., 1992; Kochut et al., 1993), and this mapping database system is the primary vehicle for the storage, retrieval, and dissemination of mapping data to the fungal genetics community. Visiting scientists have the option of making their data available to the Fungal Genetics Community by means of FGDB. His research interests include database design and query driven simulation. He has been funded by NSF to develop new mapping algorithms integrated into FGDB, and is currently funded by NIST in a large federal workflow database for the federal government.

Mr. Rinaldo DiGiorgio is a systems engineer and computer consultant. As a consultant he developed a graphical user interface and simple database system for mapping projects for PCs and UNIX systems. His role in the project is to assist in the development of graphical user interfaces. His tool, ODS, provides a means for fungal researchers to access mapping data on local machines without a network connection to the Internet.

The faculty in the databases core are E. Kraemer/UGA, J.A. Miller/UGA, W.D. Potter/UGA, C. Staben/UKY, .

k. Education Core: The role of the Education Core is to promote:

1. science as a multidisciplinary way of knowing

2. creation of materials/products to disseminate genomics and its interdisciplinary approach to fundamental and wide range of fundamental problems in biology

3. teachers using the materials/products as a medium for inservice activities with other teachers.

4. teachers and students working together to encourage students to participate in science careers.

5. human diversity in science.

Dr. Steve Oliver/UGA, associate professor of science education, and Dr. Cathy Loving/A&M are associate directors of the Education Core. Dr. Steve Oliver is currently funded by the National Science Foundation to promote precollege teacher enhancement in the sciences with a summer workshop. Core activities include developing curriculum materials and tools for precollege teachers to exploit the knowledge infrastructure about Neurospora crassa, summer workshop for precollege teachers and students, establishing research experiences in fungal genomics for precollege teachers and students, and summer programs for underrrepresented groups in science and mathematics.

Other faculty in the education core are W.W. Anderson/UGA, G. Dean/UC, T. Hagen/UGA, T. Kokoski/UNM, S.R. Kushner/UGA, G. Markle/UC, C. Mims/UGa, J.P. Oliver/UGA, J.S. Oliver/UGA, and J. Wilson/UGA.

l. Technology Transfer Core: The role of the Technology Transfer Core is to :

1. transfer of the knowledge infrastructure into industry

2. commercialize new genomics technology and experimental approaches

3. teachers using the materials/products as a medium for inservice activities with other teachers

4. to attract new industrial partners to Georgia interested in Fungal Genomics.

5. to promote human diversity in industrial sciences

6. continuing education for industrial scientists.

Dr. Cliff Baile/UGA, professor of animal science and assistant to the Vice President of Research, is associate director of the Technology Transfer Core. The Technology Transfer Core promotes partnerships with industry in fungal genomics. Dr. Baile heads this effort, and he is overseeing the creation of a $4 million dollar incubator facility (linked to the $20 million AGTR Building) to support this activity. He began as an assistant professor at Harvard from 1966-1971. He was Director of Research and Development - Animal Sciences Division, Monsanto 1982-1995. He has over 200 publications. He holds 16 patents.

Faculty in the technology transfer core include Drs. L. Ljungdahl/UGA, K.-E. L. Eriksson/UGA, J. Wild/A&M.

m. Administrative Core. The role of the Administrative Core is to:

1. place laboratory orders;

2. perform accounting for FGR;

3. schedule weekly training seminars;

4. make travel arrangements for visiting scientists;

5. manage the monthly newsletter on the Bionet and in direct mailings;

6. assemble manuals and documentation in the use of the resource;

7. assemble grant proposals to maintain FGR;

8. distribute mapping software to the fungal genetics community.

9. manage the summer workshops.

Linda Rice Lee is the systems specialist in charge of the Administrative Core. She assembled the manual for our mapping software, put together this proposal, and currently is the first point of contact for researchers interested in utilizing resources on the STC.

n. Institutional Commitment: The participating institutions has made a substantial and ongoing commitment to the STC. They are providing at least a $10 million dollar match on the proposed request for $20 million from NSF (see Matching Letter). Over the last six years they have provided salary support for Dr. Prade, Professor Wang, Mr. Griffith, and other personnel that has ensured that we retained these talented individuals. They are to provide in excess of $2.4 million in equipment over the first three years of the project.

o. Continuing Operation of the National Science and Techology Center for Fungal Genomics (STC)). The salaries of participating faculty are paid by the participating universities. Salaries of key personnell like Mr. Brown/UGA and Mr. Griffith/UGA are being provided by the Office of the Vice President for Research at UGA, College of Agriculture, School of Forestry, and College of Education over the the five years. Activities within the STC are currently supported by 5 NSF grants, 1 USDA grant, and 1 NIH grant as well as grants from other sources. Supplies, maintenance of FGR, and expenses are expected to be covered by federal grants to researchers utilizing the facility, as with BSCR. It is anticipated that all supplies used by visiting researchers will be provided by FGR and charged back to the researchers. The annual operating expenses for the facility of $115,000 (detailed below) per year for supplies, equipment, and maintenance are expected to be paid for by Federal Grants of researchers utilizing FGR, as with the Molecular Genetics Instrumentation Facility (MGIF); see Facilities.

p. The Anticipated Operating Budget. The annual operating expenses for the facility are expected to be $4,000,000 per year from NSF with allocation by activities shown below in the first year:

Activities $ millions

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1) Structural Genomics (Sequencing) 2.04

2) Functional Genomics .6

3) Evolutionary Genomics .0

4) precollege sceince/math education .6

5) undergraduate education .06

6) graduate education .6

7) administration .1

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q. Merit-based Budget Allocation scheme, The Action Committee unanimously voted to accept a merit-based annual reallocation process.

Step 1) In consultation with the External Advisory Board, the Action Committee will make yearly budget allocations by activity. The activities below are those anticipated in the first year of the project. In principle this allocation across activities can be done independently of institution: $ millions

1) Structural Genomics (Sequencing) 2.04

2) Functional Genomics .60

3) Evolutionary Genomics .00

4) precollege science/math education 0.60

5) undergraduate education 0.06

5) graduate education 0.60

6) administration 0.10

The pool of money will be provided by NSF, and the annual allocation is expected to be ~$4 million each year for the whole STC. The allocations are indirect + direct costs. The indirect costs would go to the institution. In reallocation the institution will lose/gain both indirect and direct costs.

Step 2) Once allocations within activities are made, then a merit-based system for allocation between institutions is used, and the final decision is made by the program director after consultation with the Action Committee.

Activity Criteria

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1) Sequencing: amount of annotated sequence

2) Functional Genomics: part of 10 page annual report to director & EAB

3) Evolutionary Genomics: part of 10 page annual report to director & EAB

4) science/math education part of 10 page annual report to director & EAB

5) undergraduate education annual competition for summer support

6) graduate education: annual competitive renewal on merit by graduate affairs committee

7) administration twice yearly review by external advisory board

1) This merit based allocation mechanism is an established one in science and used by all federal funding agencies. 2) This mechanism is something an administrator will readily understand because the same kind of process is used within most colleges to settle allocation issues between departments. 3) Each institution will provide a 10 page annual report summarizing its activities and how its budget was allocated between these activities.

Step 3) In that the purpose of the proposal is to create genomics infrastructure at several institutions, a base allocation of $600,000 per year will be always made to each host institution. This will ensure that infrastructure put in place by the STC will continue to act as support for genomics activities at all institutions. This floor will also allow room for merit-based reallocations. The reallocation each year will involve $1.0 million (direct + indirect costs) or 25% of the funds provided by the NSF.

r. Fees for Use of STC. Based on the projected operating budget, the per diem charge for utilizing FGR willt be $456 for varied robotics systems other than those for sequencing; however, A 5 megabase chromosome would require approximately 100 probings to generate a 29 kb resolution map. On the robotics system this project could be completed in two weeks at a cost of $6384 to a visiting scientist. Use of sequencing automation will utilize established fee structures in the NSF-funded Molecular Genetics Instrumentation Facility.

s. Space. A total of 5000 square feet are allocated for the project in the 3-year-old Life Sciences Building which houses the Departments of Biochemistry and Genetics. The Arnold Genome laboratory of 2000 sq. ft. is a fully equipped molecular genetics laboratory which scientists will have access to in addition to the robot (see Facilities). Other robotics instrumentation will be located in the 3000 sq. ft. Molecular Genetics Instrumentation Facility (MGIF) in the same building.

t. Joining and Leaving the STC. The protocol for adding and subtracting people to and from the STC is:

1) to provide a letter to the STC director indicating with whom she/he will be working and what she/he will be working on;

2) to provide a CV

3) for the Action Committee to recommend/not recommend the acceptance of the candidate and vote on that recommendation.

Once accepted the candidate will interact with the center by participating with his/her group of expertise. There can be no duplication of effort in the STC, and all research in a determined area must be coordinated. For example, this means that potential members of the functional genomics core must must interact and coordinate their efforts with the associate directors of the functional genomics core, for example.

If annual updates are not provided to the CV, current and pending support, and students and postdoctoral fellows trained, then the faculty member will be dropped from the list of faculty.

Faculty that are not at the participating institutions (i.e. A&M, UC, UGA, UNM, and Dartmouth) are not on the training grant faculty, unless specifically requested and approved by the AC.

t. Weekly Resource Meetings. A biweekly FGR "laboratory" meeting is scheduled on Thursday mornings at noon, which visiting scientists will be encouraged to attend. These meetings will provide a forum for troubleshooting experimental problems, receiving feedback on their own work by presentations to those at FGR, and serving as a training function in the use of FGR. In addition there are monthly meetings of the bioethics core and weekly meetings of the computer algorithms group.

n. Newsletter. A newsletter is posted on the Bionet and by regular monthly mailings to interested parties. Visiting scientists and recent visitors will be invited to communicate their findings about the resource and their research in the FGR newsletter.

o. Announcing Availability of Resource. A World Wide Web home page is established, and postings are made to the Bionet. Direct mailings are made to: (i) Fungal Genetics Stock Center mailing list; (ii) genomics community mailing list; and (iii) Genetics Society of America mailing list. Announcements will continue to be made in Science and Nature.