A functional genomics screen identifying blood cell development genes inDrosophilaby undergraduates participating in a course-based research experience

Abstract

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

The Endosomal Sorting Complex, ESCRT, has diverse roles in blood progenitor maintenance, lineage choice and immune response

“…Under steady state conditions each primary lobe harbors approximately 0-10 crystal cells, while they are generally absent from posterior lobes, even upon immune challenge [16]. As seen earlier, 8 of the 13 indicates that the majority of the ESCRT components are not involved in suppressing lamellocyte differentiation in the refractile posterior progenitors at steady state. However, it is likely that KD progenitors may be more sensitive to immunogenic cues as compared to normal, unperturbed progenitors.…”

“…Previous genetic screens and knockout-based functional analyses in both Drosophila and mouse models showed a role of ESCRT in maturation of specific blood cell types in erythroid and lymphoid lineages and a possible functional link of ESCRT to blood cell homeostasis [6][7][8]. Several key endosomal proteins such as Rabex5, Atg6, Rab5 and Rab11 actively control endocytic trafficking and are implicated in developmental signaling and blood cell homeostasis [9][10][11][12][13]. The blood cell-enriched conserved endosomal regulator of hematopoiesis, Asrij interacts with ADP Ribosylation Factor 1 (ARF1-GTP), regulates the endocytic proteome and maintains stemness of blood progenitors in the Drosophila lymph gland [14].…”

Fly-CURE, a Multi-institutional CURE usingDrosophila, Increases Students’ Confidence, Sense of Belonging, and Persistence in Research

“…In comparison with traditional apprenticeships, CUREs not only reach more students, but also represent a more inclusive approach to research (3, 12). Student participation in CUREs has been shown to enhance critical thinking skills (10, 13), increase learning gains, bolster scientific identity (14, 15), and increase interest in science and scientific research (16). Each of these outcomes is likely an important factor driving the positive correlation between student participation in CUREs and increased STEM retention rates, including for underrepresented minority students (11, 17, 18).…”

“…Faculty at Primarily Undergraduate Institutions (PUIs) typically have a heavy teaching requirement (teaching 3-4 classes per semester is not uncommon) that often comes with the additional expectation of research productivity (19). CUREs provide such faculty with an opportunity to combine teaching and research into a single endeavor that can, when properly structured and implemented, produce publishable work (both research data collected/analyzed by the students and pedagogical data measuring the impact on students) (16, 17, 20, 21). However, setting up a successful CURE comes with many challenges, the largest of which is typically the identification of a research project that is feasible for undergraduates working within the confines of a laboratory course (meeting 1-2 times per week, 3-5 hours total), budget-friendly, and longitudinally sustainable.…”

A cost-free CURE: Using bioinformatics to identify DNA-binding factors at a specific genomic locus

“…Not only do CUREs involve many more undergraduates in research than the traditional “apprentice” model, but they also allow faculty (especially those with high teaching loads) to make research progress. For example, the instructor of a CURE course can perform a screen (5, 6), follow up on an interesting result from their lab (7), or increase the rigor and reproducibility of a research project through replication by different lab groups or sections.…”