Browsing by Author "Lees, N. Douglas"

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    Aerobic Uptake of Cholesterol by Ergosterol Auxotrophic Strains in Candida glabrata & Random and Site-Directed Mutagenesis of ERG25 in Saccharomyces cerevisiae
    (2012-09-27) Whybrew, Jennafer Marie; Bard, Martin; Lees, N. Douglas; Blacklock, Brenda
    Candida albicans and Candida glabrata are opportunistic human pathogens that are the leading cause of fungal infections, which are increasingly becoming the leading cause of sepsis in immunosuppressed individuals. C. glabrata in particular has become a significant concern due to the increase in clinical isolates that demonstrate resistance to triazole antifungal drugs, the most prevalent treatment for such infections. Triazole drugs target the ERG11 gene product and prevent C-14 demethylation of the first sterol intermediate, lanosterol, preventing the production of the pathways end product ergosterol. Ergosterol is required by yeast for cell membrane fluidity and cell signaling. Furthermore, C. glabrata, and not C. albicans, has been reported to utilize cholesterol as a supplement for growth. Although drug resistance is known to be caused by an increase in expression of drug efflux pumps, we hypothesize a second mechanism: that the overuse of triazole drugs has lead to the increase of resistance by C. glabrata through a 2-step process: 1) the accumulation of ergosterol auxotrophic mutations and 2) mutants able to take up exogenous cholesterol anaerobically in the body acquire a second mutation allowing uptake of cholesterol aerobically. Two groups of sterol auxotrophic C. glabrata clinical isolates have been reported to take up sterol aerobically but do not produce a sterol precursor. Sterol auxotrophs have been created in C. glabrata by disrupting different essential genes (ERG1, ERG7, ERG11, ERG25, and ERG27) in the ergosterol pathway to assess which ergosterol mutants will take up sterols aerobically. Random and site-directed mutagenesis was also completed in ERG25 of Saccharmoyces cerevisiae. The ERG25 gene encodes a sterol C-4 methyloxidase essential for sterol biosynthesis in plants, animals, and yeast. This gene functions in turn with ERG26, a sterol C-3 dehydrogenase, and ERG27, a sterol C-3 keto reductase, to remove two methyl groups at the C-4 position on the sterol A ring. In S. cerevisiae, ERG25 has four putative histidine clusters, which bind non-heme iron and a C-terminal KKXX motif, which is a Golgi to ER retrieval motif. We have conducted site-directed and random mutagenesis in the S. cerevisiae wild-type strain SCY876. Site-Directed mutagenesis focused on the four histidine clusters, the KKXX C-terminal motif and other conserved amino acids among various plant, animal, and fungal species. Random mutagenesis was completed with a procedure known as gap repair and was used in an effort to find novel changes in enzyme function outside of the parameters utilized for site-directed mutagenesis. The four putative histidine clusters are expected to be essential for gene function by acting as non-heme iron binding ligands bringing in the oxygen required for the oxidation-reduction in the C-4 demethylation reaction.
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    Conducting Effective Faculty Annual Reviews: A Workshop for Academic Leaders
    (AAMC, 2015-11) Lees, N. Douglas; Palmer, Megan; Dankoski, Mary; Family Medicine, School of Medicine
    Most if not all medical schools require annual performance reviews to be conducted on all or a subset of the faculty. Despite this being a common and recurring job expectation for academic leaders such as department chairs and division directors, such leaders are often poorly prepared to conduct effective reviews. Some of the difficulties stem from lack of training, avoidance of confrontation, lack of role modeling, and the time-consuming and high-stakes nature of the process itself. In addition, administrators report challenges related to insufficient methods for assessing teaching and research, variability in evaluation processes and criteria, and a disconnect between evaluation and salary. Thus, for some academic administrators, the faculty annual review can be perceived as a burden. This 2.5-hour workshop provides academic leaders an opportunity to engage with others about faculty annual reviews so they can have more confidence and resources when engaging in the evaluation process. This resource includes materials related to a leadership development workshop on this topic. The workshop is designed for academic leaders with responsibility for monitoring and assessing the performance of faculty, such as department chairs and division directors. The overall goals of the workshop are to improve the preparation of academic leaders in conducting reviews that provide constructive feedback to faculty members regarding their overall performance and to increase academic leaders’ awareness of and capacity in the use of annual reviews as a means toward increased faculty vitality. Although few attendees submitted formal program evaluations, the workshop was well received when offered at our institution. Six evaluations were submitted from the 18 institutional leaders who attended the workshop. Though few in number, the comments received on the program evaluation indicate a positive response and that our objectives were met. All attendees noted that they were able to identify something they planned to act upon.
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    Dean, Chairs, and Faculty: A Team Approach for Enhancing Faculty Diversity
    (Wiley, 2017) Rhodes, Simon J.; Lees, N. Douglas; Biology, School of Science
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    Faculty Talent Development Effort: Mentoring Academy
    (Office of the Executive Vice Chancellor, IUPUI., 2014-04-24) Williamson, Gail; Lavitt, Melissa; Welch, Julie; Grove, Kathy; Lees, N. Douglas; Upton, Thomas; Carpenter, Janet
    IUPUI’s Strategic Plan, “Our Commitment to Indiana and Beyond,” places faculty and staff talent development among its highest priorities. The goal is to position IUPUI as an “employer of choice” through a number of actions, including improved workplace culture and communication and more robust developmental opportunities across all categories of faculty and staff. Based on feedback received during the strategic planning process, the completed implementation plan will articulate career paths for staff and faculty, identify and inventory a variety of campus resources, and provide relevant professional development opportunities. In addition, policies and procedures will be created to foster work/life balance and flexibility for IUPUI’s entire workforce. In order for IUPUI to reach the level of excellence expected in the plan, we must be assured that our investment in faculty will lead to greater success and productivity. The Mentoring Academy goals and objectives outlined below provide a means to engage faculty within each school and create a pathway for achievement of successful mentoring.