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Innovations in Undergraduate Chemical Biology Education Aaron R. Van Dyke, Daniel H. Gatazka, and Mariah M. Hanania ACS Chem. Biol., Just Accepted Manuscript • DOI: 10.1021/acschembio.7b00986 • Publication Date (Web): 01 Dec 2017 Downloaded from http://pubs.acs.org on December 3, 2017

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ACS Chemical Biology

Innovations in Undergraduate Chemical Biology Education Aaron R. Van Dyke*, Daniel H. Gatazka and Mariah M. Hanania

Department of Chemistry and Biochemistry, Fairfield University, Fairfield, CT 06824, United States

* Corresponding Author: 1073 N. Benson Road Fairfield University – BNW315 Fairfield, CT 06824 Phone: 203-254-4000 E-Mail: [email protected]

ACS Paragon Plus Environment

ACS Chemical Biology 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ABSTRACT Chemical biology derives intellectual vitality from its scientific interface: applying chemical strategies and perspectives to biological questions. There is a growing need for chemical biologists to synergistically integrate their research programs with their educational activities to become holistic teacher-scholars. This review examines how course-based undergraduate research experiences (CUREs) are an innovative method to achieve this integration. Because CUREs are course-based, the review first offers strategies for creating a student-centered learning environment, which can improve students’ outcomes. Exemplars of CUREs in chemical biology are then presented and organized to illustrate the five defining characteristics of CUREs: significance, scientific practices, discovery, collaboration and iteration. Finally, strategies to overcome common barriers in CUREs are considered as well as future innovations in chemical biology education.


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Bachelor degree recipients in chemistry, biochemistry and chemical biology join companies and graduate programs that are increasingly globalized, interdisciplinary and diversified. To better prepare students for these contexts, several national reports have called for (1) cross-disciplinary courses that give undergraduates a realistic sense of how science is conducted, (2) meaningful implementation of active learning strategies to create a studentcentered learning environment and (3) substitution of traditional, verification laboratory exercises with research-based laboratory experiences. 1, 2, 3, 4, 5 These recommendations also recognize that undergraduate research improves STEM graduation rates,6 boosts students’ selfconfidence and builds transformative mentoring relationships. 7 , 8 Research experiences are particularly

beneficial

for

retaining

first-generation

undergraduates,

women

and

underrepresented minorities in STEM fields.9, 10 The ACS Committee on Professional Training (CPT) identifies undergraduate research as a critical element of a bachelor’s curriculum. 11 Readers interested in different models of undergraduate research as well as the broad opportunities and challenges presented by it will find an excellent treatment of the topic in publications by the National Academies of Sciences, Engineering, and Medicine and the National Research Council. 5, 12 Despite the benefits of undergraduate research and its designation as a high-impact teaching practice,13 the reward structures within academic institutions frequently tempt faculty to pursue their teaching and scholarship as mutually exclusive endeavors. The purpose of this review is to illustrate how faculty can advance their research program by curricular partnerships with undergraduate students, a model known as course-based undergraduate research experiences (CUREs). This review begins by discussing effective instructional practices for creating a student-centered learning environment, an important foundation for CUREs as they are course-based experiences. The review then profiles innovative CUREs in chemical biology, emphasizing those with undergraduate co-authored publications. These exemplars have also been selected and organized to illustrate the five defining characteristics of CUREs:



demonstrating significance beyond the classroom, employing scientific practices, discovering new knowledge, collaboration and iteration. 14 Finally, strategies to overcome common barriers to the implementation of CUREs will be discussed.

DESIGNING A STUDENT-CENTERED COURSE Historically, undergraduate research experiences (UREs) have mimicked the graduate apprenticeship model. The mentoring relationships built in UREs can be transformative, inculcating students with the habits of a scientific mind (i.e. patience, independence, initiative)15 and making them more likely to attend graduate school. 16, 17 Despite the power of UREs, they are limited by scale (small student to faculty ratio) and often privilege experienced over novice students (Figure 1). CUREs represent a scalable solution, increasing access to undergraduate research while simultaneously integrating a faculty member’s teaching and scholarship. Because CUREs are courses, it is important they maximize student learning. Disciplinebased education research (DBER) in the natural sciences reveals that students learn best when instructors cultivate a student-centered environment. 18, 19 A chemical biology course designed around this principle, focuses less on what a chemical biologist knows and more on how a chemical biologist thinks. The outcomes of student-centered learning are significant, including greater student engagement, better performance on summative assessments (i.e. quizzes and exams) and a higher retention of STEM majors.20, 21 Importantly, no single activity or technology creates a student-centered classroom. Rather, such classrooms result when teacher-scholars 1) set learning objectives, 2) use formative assessments to gauge students’ comprehension, 3) adopt active-learning strategies to scaffold students’ learning (Figure 2) and 4) evalute students’ mastery of course content with summative assessments. 18, 22 Effective instructors set learning objectives for students, specific competencies they will achieve by the end of an experience (i.e. unit, lab, course). Learning objectives demystify the


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purpose of the learning experience, support the development of a schema for learning and students’ ability to build comprehension. Because students’ prior knowledge affects their level of comprehension, it is critical that instructors assess this background in order to present material at an appropriate level. Formative assessments are very useful in this respect, providing feedback to both the student and the instructor without affecting a student’s grade. Several of the active-learning strategies in Figure 2 can become formative assessment tools when used to check for student comprehension. For example, an online video illustrating a laboratory technique becomes formative assessment when punctuated with conceptual checkpoints using the free-application EdPuzzle;23 students must demonstrate their comprehension by correctly answering a checkpoint question before the video will resume. Effective teacher-scholars also recognize that students are not passive receptacles but rather learn best when they take an active role in constructing knowledge.24, 25 Thus, the highest impact learning activities are those that are scaffolded, wherein teachers provide instructional support to build on students’ prior knowledge, support their learning and minimize misconceptions. As student proficiency grows, the scaffolding is removed. Scaffolding is commonly used in project-based laboratory curricula where students begin with highly detailed experimental procedures but evolve to develop their own protocols by the end of the course. Examples of scaffolded learning from CUREs profiled in this review include analyzing published synthetic protocols to guide students through limiting reagent calculations 26 and practice problems to build proficiency in genome annotation before annotating Drosophila chromosomes. 27

Finally, formal assessments such as quizzes and exams reflect students’ mastery of learning

objectives and are one measure of students’ growth. The active learning methods in Figure 2 function best when context factors such as class size and student background are taken into consideration. For example, Process Oriented Guided Inquiry Learning (POGIL) may be well suited to a smaller sized course because of the need for frequent faculty check-ins, while concept inventories or computer simulations could



easily be scaled to a course with over 200 students. Additionally, case studies from the primary literature may work well for upper division students where as case studies from the popular media may be more appropriate for less experienced first-year or non-major courses. Above all, pedagogical methods require iterative testing, evaluation and refinement, just like any experimental method would be systematically optimized. A student-centered course can evolve over time, by changing a single unit or topic. These considerations are critical for designing an effective course that moves students from content memorization towards critical thinking, a core skill of successful researchers.

DEFINING CHARACTERISTICS OF CUREs

CUREs – Significance Beyond the Classroom CUREs provide teacher-scholars an opportunity to bring their research into the curriculum and in so doing illustrate to students its significance beyond the classroom’s walls. This can increase students’ motivation and engagement in the laboratory, particularly when paired with a tangible output of the research project. While peer-reviewed publications are often a goal of CUREs, many outcomes can extend beyond the classroom, such as student presentations at scientific meetings, contributions to curated databases such as SEAPHAGES28 or the Minimum Information about a Biosynthetic Gene cluster (MIBiG) 29 as well as the generation of evidence-based recommendations for community action. 30 With outcomes from publication to public engagement, CUREs can benefit faculty research programs and positively contribute towards promotion and/or tenure.31 The scientific significance of CUREs have been recognized by private and public funding agencies. The NSF has funded chemical biology-related CUREs including Bioorganic Chemistry of Eumelanin,32 Bioluminscent Tools for Visualizing Disease33 and Fluorinated Reporters of Protein-Protein Interactions.34 The Howard Hughes Medical Institute (HHMI) has also funded several chemical biology CUREs:


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STEMCats,

35

Endophyte and Natural Products Discovery

36

and Chemical Biology for

Sophomores. 37 One of the most extensive CURE programs is the HHMI-sponsored SEAPHAGES program, which served more than 3,400 mostly first-year students from over 140 different colleges and universities in 2017.28 The SEA-PHAGES program has generated 31 publications to date, 21 of which include undergraduate co-authors. This program, in which students isolate and characterize bacteriophages from local environments and annotate the phage genomes, introduces biological and genetic concepts relevant to chemical biology students across the country early in their college careers. Thus, CUREs are a gateway for students into research and provide valuable training for subsequent UREs.

CUREs – Employing Scientific Practices The second hallmark of CUREs is their use of scientific practices: reading the primary literature, proposing hypotheses, building and testing models, gathering and analyzing data, navigating the ambiguity of real-world data as well as developing and critiquing interpretations of one’s findings. A scaffolded research experience can help undergraduates gain research independence. Consequently, a CURE need not attempt to cover all scientific practices with students but rather meaningfully cultivate a few; the specific practices should be communicated to students through the course’s learning objectives. Brandeis University has developed a CURE where students have synthesized a library of peptide-based inhibitors for metalloproteases,26 a class of enzymes involved in HIV, Alzheimers’s disease and Crohn’s disease.38 Diversity in the library revolves around natural and unnatural amino acids, joined to a metal chelating hydroxamic acid. As an example of scaffolded learning, students were taught to write experimental protocols through a guided exercise using successful examples from the peer-reviewed literature. Students’ investment in literature-based protocols resulted in more thoughtful and independent work in the laboratory. They also honed structure determination skills, using 1H-NMR spectroscopy to characterize the



products synthesized. Finally, students strengthened interpersonal competencies including teamwork, writing ability and oral communication. McMaster University redesigned an undergraduate laboratory to explore the plasticity of ActR regulation by a catalog of anthraquinone derivatives.39 ActR is a transcriptional repressor in bacteria. The McMaster CURE is a tour de force for undergraduate chemical biology laboratory techniques. Students utilized a Diels-Alder cycloaddition to both construct the anthraquinone core and generate diversity within their chemical catalog (Figure 3A). After purifying and characterizing the small molecules, students expressed and isolated ActR. Four of the six anthraquinone derivatives exhibited modest binding to ActR (Kd = 0.14 µM to 1.70 µM), in an in vitro fluorescence assay.40 Hammett analysis indicated a subtle electronic effect with the 4-methoxy derivative being the most active. Despite in vitro binding, the anthraquinone catalog did not exhibit activity in an in vivo bioluminescence assay. A lack of in vivo activity is a common but unfortunate reality of research – especially in chemical biology – providing students an opportunity to iterate the project and teach resiliency, a lesson that should be learned early in their development as scientists.41

CUREs – Discovering New Knowledge The third hallmark of CUREs is the discovery of new knowledge. The outcome of the project should be unknown for both the student and the instructor. This differs from inquirybased labs where the outcome is only unknown to the student or the research is of little interest to the scientific community. CUREs require that students gather background knowledge on their research topic and exercise evidence-based reasoning to move the project forward. Two CUREs, one at Yale University and one at Haverford College, exemplify the discovery of new knowledge. Endophytes are symbiotic fungi or bacteria that live within plants. They offer a rich source of natural products, fueling undergraduate discovery for Yale and its collaborators over the past 15 years.36, 42 Recently, students cultivated fungal endophytes from


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Ecuador

that

produce

unique

unsaturated

hydrocarbons

43

and

hold

promise

for

bioremediation.44 Bioactivity-guided fractionation of fungal isolates lead to the elucidation of two novel sesquiterpene-polyol natural products – Stelliosphaerols A and B – with activity against Staphylococcus aureus.45 Yale undergraduates are also contributing to our understanding of the biosynthetic machinery behind the production of these secondary metabolites. They helped discover the first fungal monoterpene synthase, important for the biosynthesis of 1,8-cineole.46 While natural products can be discovered by their activity, 47 genome mining is a companion strategy wherein candidate biosynthetic gene clusters (BGCs) are identified, expressed and tested for the production of natural products.48 Undergraduate researchers at Haverford College are providing new insights into the evolution of BGCs. Focusing on type II polyketide synthase (PKS), they discovered that 5 core genes expanded and contracted during evolution. 49 These changes inform our understanding of the structural evolution of polyketide natural products such as the tetracyclines. Studying gene swaps also provides insight into the chemical diversity of natural product space and is instructive for reengineering BGCs for the production of “unnatural” natural products.50 Furthermore, this evolutionary analysis could be applied to other BGCs or be used to retrieve extinct natural products. The success of future genome mining efforts depends on a robust and curated catalog of BGCs for experimentally-validated natural products. While several databases connect bacterial

gene

ClusterMine360

clusters 52

),

with

similar

their

resulting

resources

for

metabolites

fungi

remain

(e.g.

DoBISCUIT

underdeveloped.

51

and

Haverford

undergraduates are contributing to this unmet need, bringing fungal BGC curation into the classroom. Students analyzed 217 peer-reviewed articles and 779 nucleotide records, assigning 197 unique fungal natural products. 53 Genomics-based CUREs, as exemplified by the Genomics Education Partnership,27 are particularly well suited for undergraduates because next-generation sequencing technologies have made the conversion of data into knowledge the rate-limiting step. 54 The Haverford-generated dataset was added to the recently established



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Minimum Information about a Biosynthetic Gene cluster (MIBiG) repository, yielding the largest collection of fungal natural product gene clusters to date.29

CURE – Iteration Bioorthogonal reactions are a cornerstone of the chemical biology toolbox. 55 This research area highlights how science is inherently iterative and builds upon existing knowledge. It is fitting then that the fourth characteristic of CUREs is iteration. Iteration takes many forms. Students may repeat or revise previous work to address challenges, gain a deeper level of understanding or rule out alternative hypotheses. Students may also be inspired by previous research as a departure point for their own creative scholarship. Undergraduate researchers at the University of Utah have enriched our understanding of the strain-promoted azide-alkyne cycloaddition (SPAAC) reaction by thoroughly profiling its reaction kinetics. 56, 57 Employing surfactants, they demonstrated that micellar catalysis could accelerate the rate of hydrophobic SPAAC substrates up to 179-fold. 58 Through iterative investigations, they determined that the SPAAC’s second-order rate constant was generally insensitive to buffer composition and ionic strength. 59 However, it responded differentially to organic cosolvents. These discoveries will inform the community’s use of this important bioconjugation reaction. Undergraduate researchers at Fairfield University were inspired by the fragmentation properties of the Staudinger ligation 60 to chemically label native enzymes. They prepared “capture-tag-release”

(CTR)

probes

by

linking

a

competitive

enzyme

inhibitor

and

benzophenone via the Staudinger’s aryl phosphine ester.61 After UV-initiated capture of the enzyme, addition of an azide-containing tag triggered the Staudinger ligation, concomitantly labeling the enzyme and fragmenting the CTR probe, restoring enzymatic activity. As a proof-ofprinciple, the CTR strategy was used to biotinylate β-galactosidase. Highlighting the iterative nature of this research, the enzyme inhibitor could be replaced with any selective protein-


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targeting small molecule, allowing labeling of other protein targets by subsequent undergraduates. In a new iteration of the Staudinger ligation, Bowdoin College undergraduates are pairing the distinctive architecture of bacterial glycomes with bioconjugation as a strategy for therapeutic intervention.62 Students have shown that peracetylated N-azidoacetylglucosamine (Ac4GlcNAz) can be selectively incorporated into the surface of the gastric pathogen Helicobacter pylori (Hp) but not mammalian epithelial cells. 63, 64 These azides were conjugated to 2,4-dinitrophenyl (an immune stimulant) via a Staudinger ligation, resulting in immune cell mediated destruction of Hp bacteria.64 The project is well suited to iterative study as changing the cargo attached to the Staudinger phosphine could enable new antibacterial strategies: photosensitizers to induce oxidative damage, 65 nanoparticles to induce thermal lysis 66 or peptides to breach bacterial membranes.67 Bowdoin College redesigned a course to investigate Hp urease, an enzyme critical for Hp colonization.68 Data indicate that students enjoyed the freedom of designing and implementing their own research projects, they strengthened their command of biochemistry concepts and gained a better understanding of how research impacts human health.68

CURE – Collaboration Collaboration is fittingly the final characteristic of CUREs, as collaboration is one of the most salient attributes of the chemical biology community. CUREs should model how teams of specialized scientists contribute their diverse skills to solve complex problems. This can be done inter-departmentally as at Brandeis University, where undergraduates in organic chemistry laboratory synthesized potential inhibitors or inducers of polyglutamine protein aggregation.69 Biology laboratory undergraduates then tested these compounds in model assays of Huntington’s disease. Students in both courses gained a deeper appreciation of how crossdisciplinary collaboration can yield scientifically significant results.



Collaboration can also be global in scale, as pioneered by Indiana University – Purdue University Indianapolis (IUPUI), in which undergraduates distributed across institutions (e.g. multiple U.S. sites, Poland, Russia, Czech Republic, Cuba) partner to discover drugs for neglected diseases. Distributed Drug Discovery (D3) involves three stages: (1) computational screening of virtual chemical catalogs, (2) chemical synthesis of drug candidates and (3) biological screening to determine drug leads. 70, 71, 72, 73 A defining feature of D3 is reproducibility, both within a site and among global sites. Reproducibility allows students to discern between “failed” experiments and opportunities for further investigation. For example, when developing a synthesis for N-acylated amino acid amides, undergraduates unexpectedly – but reproducibly – observed hydrolytic cleavage with electron rich acyl groups. This led to a systematic investigation of the structural elements contributing to this cleavage and ultimately conditions to minimize it. 74 Importantly, without reproducibility, these low yielding reactions might have been dismissed as outliers. To date, D3 undergraduates have developed six robust solid-phase protocols for combinatorially synthesizing (Figure 3B) natural and unnatural amino acid derivatives (Figure 3C).

75

They are screening student-synthesized molecules against

Pseudomonas aeruginosa, a major cause of lung infections in people who have cystic fibrosis.76 Excitingly, they have identified several potent inhibitors, on par with the antibacterial agent tobramycin. 77, 78 Importantly, D3 is not limited to synthesizing amino acids and their derivatives. Undergraduate researchers at Santa Clara University have used the methodology to combinatorially construct arylopeptoids (Figure 3D), 79 a promising new class of peroxisome proliferator-activated receptor (PPAR) γ agonists. 80 As chemical biology continues to break down disciplinary barriers, D3 is breaking down barriers to collaboration and offers a transformative new model for undergraduate research.


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OVERCOMING COMMON CURE BARRIERS A significant barrier to implementing a CURE is selecting an appropriate research project. It is instructive, therefore, to consider the qualities of successful CUREs. First, they employ reliable protocols that are easily learned and performed by undergraduates. Examples from this review include robust synthetic transformations (i.e. bioorthogonal reactions, peptide coupling, Diels-Alder reaction), culturing phages or genome annotating procedures. Second, the laboratory protocols in a CURE should be amenable to the timescale of undergraduates, working in three to four hour blocks per week with discrete stopping points that yield stable and storable (physical or digital) intermediates. Third, successful CUREs are designed to rapidly generate data and scale well with student class size. Consequently, preparing libraries (chemical or mutant) or contributing to information libraries are ideal approaches because they give students ownership over their individual contribution yet benefit from the aggregate data generated by the larger group. Finally, an entire project does not need to become a CURE, there may be one aspect that is particularly well suited to undergraduate adaptation. Once designed, it is ideal to pilot the CURE with a small section of students. This “soft open” is an opportunity to gather student feedback, troubleshoot aspects of the protocol and prepare activities to further scaffold students’ learning, helping them make connections between the research and their coursework. This extra investment of time will make the larger rollout of the CURE more likely to meet with scientific success. Not all barriers facing CUREs are purely scientific. For example, limited institutional resources may prevent faculty from making innovative changes to their curriculum. Joining a CURE network (i.e. SEA-PHAGES, Genomics Education Partnership) can be an effective strategy for overcoming this barrier. CURE networks often provide training for new members, practical resources like IRB approval letters and assessment tools as well as an online network of peer-scientists to help analyze data and troubleshoot problems. Faculty may also have



success targeting internal grants specifically earmarked for curricular innovation, as undergraduate research is a high-impact teaching practice.13 A well-planned and well-funded CURE can still face barriers from students, because it is an unfamiliar mode of learning. Furthermore, the unpredictable nature of research and the possibility of research “failure” can be worrisome for students who want to cultivate a high GPA for competitive fellowships and graduate programs.5 Three strategies to address students’ research anxieties include: articulating learning objectives, building undergraduate research teams and deploying conceptual checkpoints. First, recall that creating a student-centered learning environment begins by setting learning objectives. Part of a learning objective is explaining to students the course’s relevance. Articulate why the course is designed as a CURE; the benefits may be self-evident to the instructor, but they are likely obscure to the student. Second, graduate students work collaboratively, drawing intellectual enrichment from their research group. Therefore, model this by putting undergraduates into research teams with specific responsibilities. When undergraduates collaborate in a meaningful way with peers it can be a formative experience, teaching them to work as part of a diverse team. Finally, deploy conceptual checkpoints throughout the course, to assess student understanding and increase student confidence. Examples may include, literature searches or written reports on background information, guided activities to check students’ mastery of a research topic or skill as well as brief group presentations. These strategies can help students discover the exciting and transformative nature of research, enabling them to fully embrace the CURE.

DIGITAL LITERACY AND THE FUTURE OF CHEMICAL BIOLOGY ACS Chemical Biology includes the byline “the community of chemical biologists” on its cover. As mentioned above, collaboration is a distinguishing characteristic of CUREs and of chemical biologists. Interestingly, today’s chemical biology undergraduates have grown up immersed in social media technologies, yet they may not realize the power of their digital


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devices for scientific collaboration and learning. To capitalize on this unrealized potential, an outcome of chemical biology CUREs should be cultivating digital literacy: the ability to use digital and information technologies to discover, create, critique and communicate information. The University of Wisconsin-Eau Claire is engaging digital literacy with undergraduates, using two free web-based programs:81 SWISS-MODEL (for homology modeling) 82 and WEBnm@ (for normal mode analysis). 83 With these tools, students hypothesized that aminoacyl-tRNA synthetases (AARSs), which are classified based on sequence and structural homology,84 could also be discriminated based on their intrinsic dynamics. Indeed, they discovered that class I and class II AARSs exhibit distinct patterns of motion within their catalytic and anticodon binding domains.85 In a separate series of investigations, students discovered that cytochrome P450 (CYP) superfamily proteins possess strong dynamic similarities, despite low sequence identity.86 The University of Warwick is also advancing digital literacy, developing a protocol that allows undergraduates to rapidly dock chemical libraries to a target protein.87 Trends in device ownership among undergraduates nationwide indicate that the future of digital literacy – and thus chemical biology education – lies in mobile devices: laptops, smartphones and tablet computers. 88 These devices have the potential to transform student learning. In the laboratory, mobile devices are already being used as digital laboratory notebooks,89 spectrophotometers90 and luminometers.91 In the classroom, student feedback is collected in real-time using mobile devices and the website PollEverwhere, obviating the need for clickers. 92 Mobile devices are even being used to orient undergraduates to ACS national meetings. 93 Undergraduates want more meaningful and creative learning experiences with mobile devices, yet a significant percentage of faculty ban or discourage their use in the classroom.88 Instead of banning devices and sending the message they are not useful tools for learning, faculty may wish to reflect on why students are tempted to use mobile devices for nonclass activities. Is it due to disrespect or a lack of engagement? If the former, such behavior should never be tolerated and handled appropriately. If the latter, however, it is worth



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considering how these devices can be leveraged to create a more student-centered learning environment. Chemical biologists and DBER faculty will benefit by collaborating, to understand how mobile devices can further improve learning. This raises an intriguing question, “Do chemical biology undergraduates possess distinctive competencies?” While the biology community

1, 2

and the ACS CPT11 have outlined

core competencies for their undergraduates, the chemical biology community has yet to do the same. Might modern chemical biologists distinguish themselves through digital literacy and it’s ability to enhance collaboration? While collaboration is not a new concept, it has undergone a digital paradigm shift. Collaboration is no longer facilitated by proximity but rather connectivity, transformed by cloud-based resources like Dropbox94 and Google Drive.95 Chemical biology, as an interdisciplinary field, is uniquely situated to model scientific collaborations enabled by digital literacy. Regardless of the specific competencies enumerated for chemical biologists, the community must continue to innovatively integrate teaching and scholarship. In this review, we have profiled CUREs as one bridge between these interfaces. Several institutions are building another bridge in the form of convergent curricula, which emphasize interdisciplinary connections in introductory courses. 96 Supporting and building new bridges will require collaboration, particularly partnerships between research intensive (R1) universities and primarily undergraduate institutions (PUI). PUI faculty are uniquely positioned to support the pedagogical growth of R1 faculty. Similarly, R1 faculty can provide instrumentation and subdisciplinary overlap that is rare in small departments. The fruits of these collaborations could spur the next wave of innovation in undergraduate chemical biology education.

ACKNOWLEDGEMENTS The authors gratefully acknowledge support from the Fairfield University College of Arts and Sciences and a Hardiman Fellowship (to D.H.G.). The authors also thank J. Belitsky, M. Kubasik and J. Smith-Carpenter for insightful discussions.


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KEYWORDS Committee on Professional Training (CPT): A committee of the American Chemical Society that promotes excellence in postsecondary education. The CPT also furthers effective practices and innovations in chemistry education. Course-based Undergraduate Research Experience (CURE): Integrating faculty-driven research questions into an undergraduate course, CUREs are defined by five characteristics: significance, scientific practices, discovery, collaboration and iteration. Digital literacy: The ability to use digital and information technologies to discover, create, critique and communicate information. Distributed Drug Discovery (D3): Undergraduates distributed across institutions partner to discover drugs for neglected diseases. D3 involves three stages (1) computational screening, (2) chemical synthesis and (3) biological screening. Formative Assessment: Also known as “low-stakes” assessment; a method of assessment that provides the student and instructor with feedback on the student’s level of comprehension, generally without affecting the student’s grade. Learning Objective: A specific skill or competency the student should master after completing a learning experience. Often beginning of the form, “At the end of this experience, students will be able toM” followed by a specific action verb or task. Student-Centered Learning: An environment that focuses less on transmitting factual information, uses active-learning strategies and frequent formative assessment so students build an understanding of the methods and principles of a discipline. Summative Assessment: A method of assessment that measures that student’s mastery of course material and used to determine the student’s grade (i.e. quizzes, exams, course projects). Undergraduate Research Experience (URE): Student research that follows the apprenticeship model in a faculty member’s lab. A student typically works in close collaboration with a mentor (i.e. faculty, postdoc or graduate student).



Figure 1: A comparison of two undergraduate research models: undergraduate research experiences (UREs) and course-based undergraduate research experiences (CUREs). Despite their organizational differences, UREs and CUREs share many outcomes in common.


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Figure 2: Eight active-learning strategies to engage students as part of a student-centered course. These practices, when thoughtfully implemented, have the ability to improve student outcomes. In the primary literature, these strategies are also referred to as “evidenced-based practices.”



A.

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Anthraquinone Derivatives O

O • 6 derivatives synthesized

1. Lewis acid O

• In vitro binding to transcriptional repressor ActR

O

2. O2

R

R

Combinatorial Synthesis in Distributed Drug Discovery (D3)

B.

Diversity Element #1

Diversity Element #2

A

B

C

a

Aa

Ba

Ca

b

Ab

Bb

Cb

• Solid-phase protocol in 2 by 3 combinatorial grid • Two diversity elements (shown in red and blue) • Up to 6 derivatives synthesized per undergraduate

D3 Amino Acid Derivatives

C. 1. R 1 X 2. Hydrolyze

O N

Ph

O

Ph

O

H N

R2

3. Neutrilize 4. R 2CO 2H 5. Cleave

O

OH R1

• In one semester, undergraduates synthesized 95 derivatives (in duplicate) • Discovered inhibitor of Pseudomonas aeruginosa

D3 Arylopeptoids

D.

O

Cl

1. R 1NH 2 2. Homologate O 3. R 2NH 2 4. Acetylate 5. Cleave

OH O O N R2

O N R1

• Undergraduates synthesized 40 derivatives • Students reported learning gains in solid-phase synthesis, data interpretation and teamwork

Figure 3: Small molecule collections synthesized by undergraduates in chemical biology CUREs. (A) Based on the anthraquinone scaffold. (B) The combinatorial solid-phase synthesis approach used in Distributed Drug Discovery (D3). (C) D3 synthesis of natural and unnatural amino acid derivatives. (D) D3 synthesis of arylopeptoids.


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