Rethinking the STEM fields: the importance of definitions in examining women's participation and success in the sciences

This study uses longitudinal data of undergraduate students from five public land-grant universities to better understand undergraduate students’ persistence in and switching of majors, with particular attention given to women’s participation in Science, Technology, Engineering, and Mathematics (STEM) fields. Specifically, the study examines patterns of behavior of women and minorities in relation to initial choice of college major and major field persistence, as well as what majors students switched to upon changing majors. Factors that impact major field persistence are also examined, as well as how switching majors affects students’ time-to-degree. Using a broad definition of STEM, data from nearly 17,000 undergraduate students was analyzed with descriptive statistics, cross tabulations, and binary logistic regressions. The results highlight women’s high levels of participation and success in the sciences, challenging common notions of underrepresentation in the STEM fields. The study calls for researchers to use a comprehensive definition of STEM and broad measurements of persistence when investigating students’ participation in the STEM fields.

Searching for knowledge in the belly of the beast: diversity, social equity and the African graduate student mother's experience in US higher education

Diversity has become a buzz word in public discourse and in educational circles. Higher education institutions in the US have increasingly used this word as a cornerstone of their mission statements and have made increasing efforts to attract students from different backgrounds. As part of the increase in diversity efforts among US colleges, is a significant rise in the number of international students. Attracting international students has become a priority for U.S. universities regardless of size or location. This study examines the intersection between the structure of American educational environment and the blended identities of African Graduate Student Mothers. Within the context of contemporary diversity efforts in US educational institutions, this study examines both the structural environments and the socio-cultural constructs that affect the experiences of African graduate student mothers. Based on a qualitative research interview design, a total of nineteen African graduate student mothers at a Mid-Western University in the US were interviewed individually and in groups over a six weeks period. Results from this study show that apart from the difficult and often dehumanizing treatment African student mothers endure from immigration and consular officials in their various countries and ports of entry, they often find themselves at the margins of their various programs and departments with very little support if any. This is because most of them enroll into graduate programs after arriving as dependants of their spouses; a process that does not allow them to negotiate for departmental commitments and support prior to their arrival. Not only do these women face racial discrimination from white professors, staff and fellow students, but they also experience discrimination and hostilities from African Americans and other minority groups who see them as threats to the limited resources that are often set aside for minority groups in such institutions.

Biosynthesis and mode of action of ribosomally synthesized and post-translationally modified antimicrobial peptides

One of the greatest sources of biologically active compounds is natural products. Often these compounds serve as platforms for the design and development of novel drugs and therapeutics. The overwhelming amount of genomic information acquired in recent years has revealed that ribosomally synthesized and post-translationally modified natural products are much more widespread than originally anticipated. Identified in nearly all forms of life, these natural products display incredible structural diversity and possess a wide range of biological functions that include antimicrobial, antiviral, anti-inflammatory, antitumor, and antiallodynic activities. The unique pathways taken to biosynthesize these compounds offer exciting opportunities for the bioengineering of these complex molecules. The studies described herein focus on both the mode of action and biosynthesis of antimicrobial peptides. In Chapter 2, it is demonstrated that haloduracin, a recently discovered two-peptide lantibiotic, possesses nanomolar antimicrobial activity against a panel of bacteria strains. The potency of haloduracin rivals that of nisin, an economically and therapeutically relevant lantibiotic, which can be attributed to a similar dual mode of action. Moreover, it was demonstrated that this lantibiotic of alkaliphile origin has better stability at physiological pH than nisin. The molecular target of haloduracin was identified as the cell wall peptidoglycan precursor lipid II. Through the in vitro biosynthesis of haloduracin, several analogues of Halα were prepared and evaluated for their ability to inhibit peptidoglycan biosynthesis as well as bacterial cell growth. In an effort to overcome the limitations of in vitro biosynthesis strategies, a novel strategy was developed resulting in a constitutively active lantibiotic synthetase enzyme. This methodology, described in Chapter 3, enabled the production of fully-modified lacticin 481 products with proteinogenic and non-proteinogenic amino acid substitutions. A number of lacticin 481 analogues were prepared and their antimicrobial activity and ability to bind lipid II was assessed. Moreover, site-directed mutagenesis of the constitutively active synthetase resulted in a kinase-like enzyme with the ability to phosphorylate a number of peptide substrates. The hunt for a lantibiotic synthetase enzyme responsible for installing the presumed dehydro amino acids and a thioether ring in the natural product sublancin, led to the identification and characterization of a unique post-translational modification. The studies described in Chapter 4, demonstrate that sublancin is not a lantibiotic, but rather an unusual S-linked glycopeptide. Its structure was revised based on extensive chemical, biochemical, and spectroscopic characterization. In addition to structural investigation, bioinformatic analysis of the sublancin gene cluster led to the identification of an S-glycosyltransferase predicted to be responsible for the post-translational modification of the sublancin precursor peptide. The unprecedented glycosyltransferase was reconstituted in vitro and demonstrated remarkable substrate promiscuity for both the NDP-sugar co-substrate as well as the precursor peptide itself. An in vitro method was developed for the production of sublancin and analogues which were subsequently evaluated in bioactivity assays. Finally, a number of putative biosynthetic gene clusters were identified that appear to harbor the necessary genes for production of an S-glycopeptide. An additional S-glycosyltransferase with more favorable intrinsic properties including better expression, stability, and solubility was reconstituted in vitro and demonstrated robust catalytic abilities.