Ethics, Rigor & Reproducibility

PLAN FOR THE INSTRUCTION IN THE RESPONSIBLE CONDUCT OF RESEARCH (RCR) 

Based on feedback from the prior proposal submission and key stakeholders on the training grant, we have now developed a more integrated training plan based on activities with other training grants on campus. A key tenant to this training is a two-year rotating series of workshops based on the “NIH guidance on required RCR training.” Our trainers will play leading roles in these trainings in collaboration with the Medical Scientists Training Program (MSTP), as well as six additional T32 training grants and the microbiology immunology and cancer biology (MICaB) program. Additional didactic training will be provided by a mandatory ethics course taken by all trainees in either the Chemistry or the Biochemistry, Molecular Biology and Biophysics (BMBB) departments. Specific lab training is also being provided by the individual trainers within their research groups and through an online training module for all new trainees and trainers. These training activities are captured in our annual report for all training grant participants and are elaborated below.

• The MSTP T32 (PI Yoji Shimizu) has been collaborating with UMN T32 training grants to offer summer Responsible Conduct of Research (RCR) workshops that meet the NIH requirements for RCR training. They have now updated these workshops to include 8 RCR workshops (1.5 hours each), with 4 workshops being offered every summer in May, June, July, and August. In addition to the MSTP, the other participating T32s are Cancer Biology (Carol Lange, PI), Immunology (Kris Hogquist, PI), Virology (Lou Mansky, PI), Aging (Dawn Lowe, PI), Comparative Pathology (Cathy Carlson, PI), and Cardiovascular Engineering (Victor Barocas, PI), the MiCAB program (Ameeta Kelekar, DGS) and our training grant. The MSTP has identified a lead faculty facilitator for each of the 8 sessions. The CBITG T32 PIs will recruit four T32 faculty members on a rotating basis to participate as a faculty discussant each year starting in the summer 2023. Co-PI Prof. Pomerantz served as the CBITG discussant this May. Each session fosters discussion, active learning, engagement, and interaction among the participants with extensive use of case studies. Feedback from workshop participation from trainees will be addressed during the annual review meeting. 

Administrative assistance is being provided by the MSTP and MICaB program for scheduling the workshops, room reservations and taking attendance. However, additional T32 administrators will be asked for assistance when needed (See Shimizu letter of support).  We will ensure that all trainers will take part in serving as a discussant on a rotating basis. Changing our RCR training from CBITG-only activities to this centralized model both increases the training that our trainees receive and decreases the overlap of effort that occurs between T32 grants on our campus. 

Workshops (12 hours in years 1 and 2 on the training grant):

• Odd-numbered years (beginning in 2023): May-August

  • Mentoring and mentor/mentee responsibilities and relationships (NIH-C), safe research environments (NIH-D) CBITG Discussant: William Pomerantz, Chemistry, completed

  • Data acquisition and analysis; laboratory tools (e.g., tools for analyzing data and creating or working with digital images); recordkeeping practices, including methods such as electronic laboratory notebooks (NIH-G) CBITG Discussant: Wendy Gordon, BMBB

  • Conflict of interest and conflict of commitment (NIH-A), intellectual property, collaborative research, including collaborations with industry and investigators and institutions in other countries (NIH-E) CBITG Discussant: Erin Carlson, Chemistry

  • The scientist as a responsible member of society, contemporary issues in biomedical research, and the environmental and societal impacts of scientific research (NIH-K) CBITG Discussant: Rick Wagner, Medicinal Chemistry

• Even-numbered years (beginning in 2024): May-August

  • Policies regarding human subjects in research, safe laboratory practices (NIH-B) CBITG Discussant: Natalia Tretyakova, Medicinal Chemistry

  • Policies regarding live vertebrate animal subjects in research, safe laboratory practices (NIH-B) CBITG Discussant: Mark Distefano, Chemistry

  • Responsible authorship, publication (NIH-J) and peer review (including the responsibility for maintaining confidentiality and security in peer review) (NIH-F) CBITG Discussant: Valerie Pierre, Chemistry

  • Research misconduct and policies for handling misconduct (NIH-I), secure and ethical data use, data confidentiality, management, sharing and ownership (NIH-H) CBITG Discussant:  Burckhard Seelig, BMBB

Centralized Training for all Trainees and Trainers (3 hours 1x initial training) 

Centralized RCR training for all new trainees and trainers will now be required through an online 3-hour course through UMN’s Collaborative Institutional Training Initiative (CITI) to augment the workshop training. 

Training topics cover 5 key areas include 1) general principles, professional and fiscal responsibilities, dealing with misconduct, and mentoring. 2) research with human participants, conflicts of interest, and workplace safety, 3) data collection, sharing, and interpretation, 4) plagiarism, authorship, and peer review, 5) responsibility to the public and safety. This training is required by the Office of Vice President of Research for all new investigators receiving sponsored research projects, and records of compliance are tracked and can be accessed electronically through a UMN-specific accessible website.

Didactic Training in Ethics.  (1 credit, Spring semester, 1st year of graduate school)

All trainees are required to take a course on Ethics and Responsible Conduct of Research. 

Chemistry and Medicinal Chemistry students:   

In the Spring semester of their first year, trainees in Medicinal Chemistry and Chemistry enroll in CHEM 8066, which is a 1 credit course: “Professional Conduct of Chemical Research”  Content is delivered through student presentations, discussion of case studies, and guest speakers on topics of RCR and ethics. Required readings have included “On Being a Scientist: A Guide to Responsible Conduct in Research,” 3rd ed. and Art of Scientific Investigation”, and “Ethics in Science: Ethical Misconduct in Scientific Research” Topics covered include: copyright and publication ethics, publication responsibilities, communication of results, peer review, adviser/advisee relationships and conflicts, and scientific misconduct. Prof. Pomerantz recently led two lectures for this course in 2021. 

Biochemistry students:   

In the Spring semester of their first year, Biochemistry Students are required to take the 1 credit course BioC 8401, “Ethics, Public Policy and Careers in Molecular & Cellular Biology”. Content is delivered through a combination of case studies, small group discussions, and lectures covering the ethics of scientific investigations including the relationship between science, culture, and public policies. Required readings have included “On Being a Scientist: A Guide to Responsible Conduct in Research,” 3rd ed. and Art of Scientific Investigation”, and “Ethics in Science: Ethical Misconduct in Scientific Research.” Topics include issues related to authorship and data handling, intellectual property and mentorship, plagiarism, and misconduct. In addition, the course analyzes the relationship between science and public policies. 

Regular Chemical Biology Colloquium Seminar Series. (1-2 per semester)

For sustained training, we will continue to provide yearly RCR and rigor and reproducibility-specific seminars through our chemical biology colloquium seminar series. Recent seminars led by our trainers have included rigor and reproducibility in data analysis, data management, and experimental design, and journal specific guidelines for publishing. We will continue to present 1-2 seminar topics per semester. 

Laboratory Safety Training

UMN has developed a strong culture of laboratory safety over the last 11 years. This includes formation of a joint safety team, which is a researcher-led organization focused on improving the culture of safety in chemical laboratories at the University of Minnesota. This initiative has gained national recognition and has been developed in partnership with industrial leaders. Every laboratory in the departments of chemistry, medicinal chemistry, and biochemistry have laboratory safety officers, and laboratories are regularly inspected for maintaining safe operating procedures for conducting research. In addition, to augment the safety culture, safety moments are regularly presented before seminars in the departments of chemistry and medicinal chemistry departments. Many of our trainers also include them in regular group meeting presentations. In addition to short rigor and reproducibility presentations at CBIG presentations, safety moments will also be interspersed as has been done previously for maintaining a culture of safety for all of our trainers and trainees. 

Summary of Training Both Formalized and within Individualized Trainer Labs: 

The RCR training covers multiple stages of the trainees’ development starting at their first year of graduate research and is implemented in several formats. Chemical biology training is diverse, and as such we have targeted a broad set of training opportunities to expose trainees to the full enterprise of biomedical research that is aligned and synergizes with their research. Formal classroom instruction is provided the first year for all graduate researchers during the academic semester with a significant focus on ethics. An online three-hour refresher module in RCR training is provided to new trainees on the grant, which would occur in years two or three of their graduate education for a new trainee. Six additional hours per year of interactive training at RCR workshops will be provided each summer for current trainees during their two years on the training grant.  Throughout the trainees’ time in our program we will also continue to provide yearly RCR and rigor and reproducibility-specific seminars through our chemical biology colloquium seminar series and CBIG talks. Finally, individualized training in RCR will continue within trainer research groups providing opportunity to reiterate and augment key elements of RCR training specific to their research and will be captured in our annual trainer surveys. Together this provides an integrated set of RCR training through multiple formats and will last the duration of the trainees’ time in our program. 

PLAN FOR INSTRUCTION IN METHODS FOR ENHANCING REPRODUCIBILITY 

Given the multidisciplinary nature of research at the interface of chemistry and biology, it is paramount that research conducted by trainees be carried out with the highest level of rigor and reproducibility (R&R). To ensure that trainees receive the highest level of training in R&R and that the training has a lasting impact, trainees will continue to participate in several training activities throughout their time in our program. Specific R&R training will include:

• Rigorous experimental design and data interpretation

• Consideration of relevant biological variables such as sex

• Authentication of key biological and/or chemical resources

• Data and material sharing

• Record keeping

• Transparency in reporting

1) As an orientation to the importance of the concepts of R&R in scientific research, all trainees will view modules 1-4 at the NIGMS training site containing modules developed for R&R training. Aspects of these training modules will be revisited during our regular chemical biology interest group (CBIG) meetings described below. These online training modules complement the RCR training modules described in the prior section  from our UMN Collaborative Institutional Training Initiative (CITI) and summer RCR workshops.

2) The department of chemistry offers a 4-credit intro to chemical biology course CHEM 8411 (currently taught by Trainer Carlson) and a second semester 4-credit Chemical Biology of Enzymes course CHEM 8412 (currently taught by Trainer Distefano). The former course is taken by the majority of our trainees, and has a significant primary literature component where data is analyzed, including statistical methods, analysis of experimental design, and exposure to various forms of biological and chemistry-specific data. CHEM 8412 specifically addresses rigorous statistical analysis, transparency and reproducibility, data processing, materials and data availability, and specific methods for kinetic analysis of enzymatic reactions. Finally, our ethics courses CHEM 8066 and BioC 8041 discussed in our RCR section and summer RCR workshops also discuss elements of R&R including transparency in reporting.

3) Each trainee along with their two advisors will develop a research plan for their proposed research during the training period that incorporates specific plans on how the key concepts of R&R are to be addressed and evaluated. Each trainee is to meet with their primary mentor at least monthly and co-mentor when relevant for receiving feedback on their research progress and adherence to R&R concepts. Each trainee will give a yearly progress report to the steering committee that includes their implementation of R&R concepts, as well as a formal evaluation of their research. The initial plans will be submitted to the steering committee and Program Directors Carlson and Pomerantz for approval with follow-up evaluation in writing on the progress reports.  Based on the ongoing review, the committee may recommend additional training for the trainee.

4) To ensure that R&R concepts are re-enforced after the two-year training period, all trainees are required to attend at least one seminar/workshop annually, offered through the Chemical Biology Colloquium (CBC) of the Chemical Biology Initiative. 1-2 seminars will be dedicated per year for discussion of topics related to RCR and R&R. Examples of recent seminar/workshops presented within the last two years are “Preventing headaches with good experimental design and data management”, “Managing and Sharing your Data”, and “Top Design Tips for Better Grant Figures”.  Several of our trainers are Editors with various journals and we will also have them provide a seminar focusing on transparency in reporting during these workshops. In addition, following completion of their 2-year training period, all trainees will present an update on their research at this seminar series, which includes direct feedback on their rigorous experimental design, data interpretation, and critical evaluation of the foundational research underlying their project. A full list of seminar topics from the prior 2 years that include R&R topics is included in the Appendix on training activities.  

5) As a new initiative, our training grant participants will continue to avail themselves of the NIH Clearinghouse resources on R&R training, which provides relevant modules and materials for discussion. We will include a short R&R interactive discussion at several seminars throughout the year. The timing for these discussions will be chosen based on the monthly chemical biology interest group (CBIG) presentations for which our trainees, postdocs, and students in the broader chemical biology community present. Prior to the start of the meeting, a short video will be played on R&R relevant topics followed by a short 10-15-minute discussion led by a CBITG trainer or student presenter. These materials have been developed through NIH supplement awards, are freely available from the NIH website, and are anticipated to promote a very focused and engaged discussion.   Three examples of modules that will be implemented will include:

• Experimental and technical replications

• Consideration of relevant biological variables such as sex

• Authentication of key biological and/or chemical resources 

In summary, our current and updated plan for instructional methods on R&R is multi-tiered, which engages both our trainees and the broader chemical biology community at UMN. This plan has been developed following the NIH guidelines for rigor and reproducibility, and uses available resources aligned with the principles of high quality research. Finally, this plan has been designed to expose trainees to R&R throughout their time in our program starting from introductory modules upon joining the T32, formal classroom instruction during their first two years in our program, and the annual program evaluation meeting.  In addition, sustained training is being provided both through direct mentor and co-mentor interactions, as well as through our regular seminars and workshops during the CBC seminar series and CBIG meetings provided regularly throughout the year.