Biology and Biochemistry 2019-2020 Research Projects

1. Biology and Biochemistry2019-2020 Research Projects * * Prof Schlessman not taking students next year.

2. O’Carroll research: Structure-Function Studies of Endogenous Retroviruses Integrated virus RT Human chromosome RT Retroviruses such as HIV have an RNA genome that is reverse transcribed to DNA, which is then integrated in the chromosome of the infected cell.

3. Retroviruses need to escape unspliced from the nucleus HIV replicates in the nucleus, but it needs to export its unspliced RNA genome to the cytoplasm to be packaged into new virus particles. HIV has evolved to produce the protein Rev, which specifically recognizes the Rev-response element (RRE) and mediates the export of the unspliced HIV genome. The RRE is an ideal drug target because it is essential for HIV replication. Integrated viral genome Human chromosome ✔ Spliced mRNA RRE Unspliced mRNA * Rev ✔ Packaging Translation

4. Human endogenous retroviruses are remnants of ancient infections • Human endogenous retroviruses (aka LTR retrotransposons) are sequences of retroviral origin that compose 8% of our genome. • Retroviral glycoproteins (ENV) have been adapted to play significant roles in development, muscle growth, and cognition. • Aberrant expression of endogenous retroviruses has been associated with cancer and autoimmune disorders (notably ALS and MS).

5. Expression of endogenous retroviral proteins depends on a functional RRE-like RNA RcRE * Goal: Perform a structure-function analysis on the RcRE to determine the structural features necessary for optimal function.

6. How can YOU help? • We will employ various biochemical and molecular biology techniques to understand HIV RNA-protein interactions. • We work with non-infectious forms of the virus to understand its biochemistry. Students will: • Learn to perform PCR mutagenesis, bacterial transformations, and other molecular biology techniques to construct mutant plasmids. • Use cell culture to assay RcRE function and Western blotting to quantify function. • Learn to analyze and interpret data and prepare poster and oral presentations.

7. Basta Lab Research Projects Combating antibiotic resistance Problem: Antibiotic resistance is an emerging global public health concern. Deaths attributable to AMR are expected to surpass other major causes of death by 2050.

8. Basta Lab Research Projects Identify essential protein Combating antibiotic resistance Problem: Antibiotic resistance is an emerging global public health concern. Deaths attributable to AMR are expected to surpass other major causes of death by 2050.

9. Basta Lab Research Projects Identify essential protein Learn as much as you can about what it does Combating antibiotic resistance Problem: Antibiotic resistance is an emerging global public health concern. Deaths attributable to AMR are expected to surpass other major causes of death by 2050.

10. Basta Lab Research Projects Identify essential protein Learn as much as you can about what it does Develop drug to inhibit protein Combating antibiotic resistance Problem: Antibiotic resistance is an emerging global public health concern. Deaths attributable to AMR are expected to surpass other major causes of death by 2050.

11. Basta Lab Research Projects Identify essential protein Learn as much as you can about what it does Develop drug to inhibit protein Kill bacterium Combating antibiotic resistance Problem: Antibiotic resistance is an emerging global public health concern. Deaths attributable to AMR are expected to surpass other major causes of death by 2050.

12. Basta Lab Research Projects Identify essential protein Learn as much as you can about what it does Develop drug to inhibit protein Kill bacterium Combating antibiotic resistance Problem: Antibiotic resistance is an emerging global public health concern. Deaths attributable to AMR are expected to surpass other major causes of death by 2050. PG Virtually all bacteria possess a peptidoglycan (PG) layer that is essential for their growth and viability.

13. Basta Lab Research Projects Learn as much as you can about what it does ·PG biosynthesis ·PG modification Develop drug to inhibit protein Identify essential protein LD-transpeptidases (Ldts) Kill bacterium Combating antibiotic resistance Project: Investigating new drug targets in rapidly growing mycobacterium (RGM) species.

14. Basta Lab Research Projects Learn as much as you can about what it does ·PG biosynthesis ·PG modification Develop drug to inhibit protein Identify essential protein LD-transpeptidases (Ldts) Kill bacterium Combating antibiotic resistance Project: Investigating new drug targets in rapidly growing mycobacterium (RGM) species. With the risk of biological warfare on the rise, strategies are needed to combat emerging biological threats! The development of new antimicrobials can contribute to warfighter protection.

15. Basta Lab Research Projects Combating antibiotic resistance So what will YOUbe doing? I want to study ALL aspects of Ldt enzymes • Molecular cloning • Protein overexpression and purification • Interpreting crystallographic data • Various microbiological techniques • Biochemical assay development LdtG 50 37

16. Sweet Lab: Aerobiotics – Drugs from Thin Air

17. Sweet Lab: Aerobiotics – Drugs from Thin Air B10 CC1 MM MGln-1 MM MGln-2 QLW11 MM MP 1 MM MP 2 QLW15 MM MP 1 MM MP 2 B10 ATT positive mode M+ m/z 1270.90 M+ m/z 1256.68 Actinomycin D

18. Sweet Lab: Isolation and study of extremophiles image credit: Charles Sweet http://usnapsp.blogspot.com/2012/04/bromex-2012-wrap-up.html Nghiem, S.V., et al., Proc. Bionature 2013 Sweet, et al., Mar. Drugs 2014, 12, 4126-4147

19. Evolutionary modulation of psychrophilic endotoxin structure Psychrobacter cryohalolentis endotoxin 12 Sweet CR, Watson RE, Landis CA, and Smith JP, Mar Drugs 2015, 13(8) 12 10 12 10 12

20. Biosurvey: psychrophiles in the Severn River

21. Leaves, Leaf Eaters, and The Chemistry That Connects Them Research in the Rehill Lab AY 2018

22. Gypsy Moth-Red Oak Projects Isolation and Identification of Red Oak Tannins (in conjunction w/ Dr. Dillner) {liquid chromatography, mass spectroscopy and NMR spectroscopy} Previously: Jacob Cole (Research Award Winner 2012), Josh Kotler, Ian Eisenhauer, Awad Mohamed , Aidan Lang 2. Feeding Studies: How do gypsy moth caterpillars respond to various tannins in their diets? {raising and handling caterpillars, statistical analysis of growth and development, dissection of caterpillars} Previously: Amanda Lau, Andrew Almonte, Adam Hammer, Amy Krick, Lianne Marquez & Erin Kusuda

23. Also… • Feeding Studies: How do leaf defenses vary within the canopy of forest trees as well as among trees at different stages of development (seedling, sapling, canopy size tree) {raising and handling caterpillars, diet preparation, statistical analysis of growth and development , leaf collection?} • Previously: Harold Hickey, Jenn Underhill, Nia Chandler, Eleanor Pratt, Nii Quaye

24. Associate Professor Daniel Morse Biological roles and regulation of A to I RNA editing Adenosine Deaminases that Act on RNA (ADARs) catalyze hydrolytic deamination of adenosines within double-stranded RNA A to I conversion changes the sequence and the structure of RNA. The biological consequences depend on the type of RNA and where editing occurs within the RNA. Figure shows possible consequences of mRNA editing.

25. How the Guanine Riboswitch Works In Vivo Adapting the Guanine Riboswitch for use In Vitro

26. Adapting the Guanine Riboswitch for use In Vitro In Vitro Selection Strategy for Changing the Specificity of the Guanine Riboswitch (Hypoxanthine; HX)

29. The Biochemistry Concentration • Requirements: • Complete all requirements for the chemistry major • Take SC336 • Take two semesters of biology (SB251 and higher) • And perform either • One year of biochemically-related independent research (SC495/496) • OR • One semester of research or Capstone and one biochemically-themed elective

30. Can projects performed with “regular” chemistry professors fulfill the requirement?Yes, if it: • Uses biochemical methods or materials (e.g. materials science studies of silk, cellulose) • Has application to a biological or biochemical problem (e.g. environmental chemistry, medicinal chemistry, natural products chemistry) • Uses chemical or computational methods to study a biomolecule (e.g. X-ray crystallography, computational studies of fluorinated peptides, biofuels) • Others? – come talk to us!