Characterizing Drosophila mutagen sensitive alleles through a collaborative Course-based Undergraduate Research Experience (CURE)

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Research Goal: map and characterize unknown mutagen-sensitive genes in Drosophila

Our collaborative project brings together experts in DNA repair and replication from multiple PUIs to map and characterize mutagen sensitive genes in Drosophila through a series of classroom research modules (only 14 of the 58 discovered mutagen sensitive genes have been genomically mapped and characterized). The collaborative nature of this project allows undergraduate students in multiple biological disciplines to contribute to collective research on the function of the mus genes.

In the past 3 years, our CURE has engaged nearly 200 undergraduate students, who have reported positive experiences and higher learning gains in these courses. Our future prospects include creating additional research modules for our CURE and expanding our network to involve additional researchers.

Faculty collaborators

Elyse Bolterstein, Associate Professor of Biology, Northeastern Illinois University
Kathryn Kohl, Associate Professor of Biology, Winthrop University
Eric Stoffregen, Associate Professor of Biology, Lewis-Clark State College
Christina Swanson, Associate Professor of Biology, Arcadia University

How we run the CURE in class

Experiments are split between different institutions based on class content and each faculty member’s area of expertise (Figure 1).
1-3 month-long research modules integrated into core undergraduate biology courses. This may include content scaffolding to also teach students about Mendelian genetics
Teams of 3-4 students develop their research question and experimental design within given parameters
Students present their results as a scientific poster and participate in a virtual poster session with the other institutes
Preliminary data is confirmed in individual faculty research labs

Figure 1: Workflow for mapping and characterizing *mus109.* *mus109* was our CURE’s first target gene and was mapped by Kathryn Kohl’s genetics classes and is currently being characterized in classes at NEIU, Lewis-Clark, and Arcadia. Future genes characterization may follow a similar design to best suit the expertise of each collaborator and best match the content of the CURE course.

Preliminary results – mus109 mapping and characterization

mus109 is a recessive, X-linked gene. There are three available mus109 alleles (mus109^lS, mus109^D1, and mus109^D2) that have been shown to be sensitive to several DNA damaging agents including ionizing radiation (γ-rays), methyl methanesulfonate (MMS), and nitrogen mustard (HN₂) (Boyd et al. 1976; Smith 1976; Nguyen et al. 1978; Mason et al. 1981).

**Figure 2:** *Mus109* was mapped to the X-chromosome and is orthologous to DNA2 (Winthrop University, Genetics). A) Deletion crossing scheme; B) Overlap of deletion mutants sensitive to MMS uncovers X-linked locus of ~62K bp; C) Of the 9 candidate genes, DNA2 is the most likely ortholog of *mus109.*

mus109 characterization

mus109 mutants are sensitive to bleomycin. Sensitivity to camptothecin, ethanol, potassium bromate, and hydroxyurea were also tested with inconclusive results. – Genetics, Northeastern Illinois University
mus109 females, but not males, are infertile. Maternally loaded mus109 is required for embryo survival. – Genetics, Lewis-Clark State College
mus109 oocytes develop abnormally. Nurse cells undergo premature apoptosis and oocyte growth is halted, which may explain female infertility. – Developmental Biology, Arcadia University

Preliminary results – learning gains

We surveyed student learning gains using a standard SALG tool and questions. We also assessed our CURE design using questions developed to provide feedback to the CURE community (Corwin et al, 2015)

CURE students in General Genetics, NEIU, Fall 2019

Next steps

Students reported that they didn’t have sufficient time to fix problems in their studies or ask follow-up questions. We plan to develop dedicated research courses so that students could have more time to repeat experiments and alter analyses based on study outcomes.
Confirm preliminary data for publication.
Grow our CURE network so that we can map more of the candidate genes and more fully characterize genes’ function through a greater variety of experiments.

We’d love to hear from other members of the fly community! Are you interested in using the mus CURE in your class? Do you have a CURE and would like to share ideas? Sign up below and we’ll get back to you. No pressure, we love to chat!