Randall Phillis - US grants

9511338 Phillis The establishment of the distinct identities of individual neurons represents a fundamental step in the development of the diverse array of neurons that make up a mature nervous system. During this process, individual nerve cells develop distinct properties including characteristic anatomy, physiology, and patterns of connectivity. However, the mechanisms that confer neuronal identity are just beginning to be understood. The goal of this research is to investigate the role of a newly discovered gene in the establishment of neuronal identity in the invertebrate peripheral nervous system. Mutations in this gene affect behavior and the morphology of adult sensory organs. In addition, these mutations have the ability to enhance the phenotype of mutations in another gene that is a regulatory gene required to confer proper identity to external sensory organs. If function in this gene is lost, the mechanosensory bristles are transformed in their identity and acquire characteristics of internal stretch receptors. When mutations are present in both genes, there is an interaction that results in the loss of nearly all of the mechanosensory bristles from adults. The effects of mutations in the gene under study on sensory organ development will be investigated using several genetic and immunological markers specific to certain types of sensory organs. This analysis will determine whether mutations in the gene result in a transformation of sensory organ identity. The gene will also be cloned and sequenced to determine the pattern of its expression and the structure of its protein product. Finally, an ectopic expression system for the gene will constructed to determine whether expression in specific subsets of sensory organs affects their development. The data from these investigations will provide fundamental insights into the genetic mechanisms that function in the development and differentiation of the peripheral nervous system.

9729649 PHILLIS Dr. Phillis's research focuses on the role of the "motor protein" dynein in neuronal development and the establishment of the mature anatomy of neuronal axons. Although dynein is well known to be involved in the movement of intracellular components along microtubules, Dr. Phillis's analysis of the gene for cytoplasmic dynein light chain, Cdlc1, in the fruitfly Drosophila has suggested a role for this molecule in shaping the growing tips of axons. This research encompasses three projects, each designed to investigate specific aspects of the cytoplasmic dynein light chain with respect to axon anatomy. The first project involves the analysis of when Cdlc1 mutations affect axon projections during development. Using a set of genetic markers, Dr. Phillis and his colleagues will label specific sensory neurons and their axons as they undergo pathfinding in the central nervous system during development. They will then characterize the development of these axons in Cdlc1 mutants, and compare them with observations of wild type development. This analysis will help determine the timing of onset of axon defects caused by Cdlc1 mutations. In addition, Dr. Phillis's group will create a mutant form of Cdlc1 that can be activated by temperature shifts. With this inducible gene, it will be possible to determine the specific time in development when Cdlc1 function is required for the establishment of proper neuronal anatomy. In a second project, Dr. Phillis's group will characterize the effects of Cdlc1 mutations on neurons grown in primary cell culture, using a microtubule labeling system that allows the analysis of microtubule dynamics in live cells. These experiments will resolve the effects that Cdlc1 mutations have on the growth dynamics of individual neurons, and on the dynamic changes in cytoskeletal architecture that underlie the growth of axon projections. Finally, Dr. Phillis's group will perform a genetic screen for mutations that either enh ance or suppress the effects of Cdlc1 mutations on axonal growth. Subsequent genetic and molecular characterization of genes identified in this analysis will provide a detailed understanding of a series of genes that function with Cdlc1 in neural development.

Approximately 700,000 college and university students enroll in introductory biology courses each year. The majority of these courses deliver the basic facts and terms of biology to large numbers of passive students. Few of these courses have learning scientific reasoning skills among their stated objectives. This project is developing a set of teaching tools and tests in biology centered around the primary learning objective of model-based reasoning (MBR), the central intellectual activity of professional biologists. The intellectual merit of the project lies in the development, evaluation, and dissemination of a set of methods and tools for teaching and testing model-based reasoning in college level introductory biology courses. An independent panel of experts, drawn from among professional biologists nationwide, is rating model-based reasoning questions. These expert ratings are compared with student performance in a classroom in which MBR problems are used for teaching and assessment. This study uses open-ended essays to investigate changes in students' descriptions of their reasoning process at several points during the course. Improvements in reasoning skills are being compared between students in MBR-based courses and traditional lecture-based instruction. A series of valid multiple-choice summative examinations designed specifically to assess model-based reasoning skills are also being developed. Model-based reasoning instruction has the potential for broad impact in introductory biology courses nationwide. It exploits the strengths of two technologies that are being widely adopted. The first is web based course support, and the second is the use of Classroom Communications Systems (personal response devices) in the lecture hall. In partnership with a major publisher, a teacher's guide and student study materials are being published.

Underrepresented minority (URM) students generally attend less selective STEM
institutions, have disproportionately low io2 nd year continuation rateslu in STEM majors,
and across all institutions regardless of selectivity or LSAMP participation achieve 6-year
graduations of <35% compared to >60% for non-minorities. In Phase I of the NE-
LSAMP we have increased the enrollment, retention and graduation URM STEM
students beyond that possible through the initiative of any single institution. As
isselectivele institutions, our Phase II work combines proven interventions (mentoring,
undergraduate research opportunities, etc) and interventions with high potential for
success (Supplemental Instruction in inbarrier courseslr, individual tracking) both to
normalize rates of URM persistence and graduation in STEM and to increase
professional/graduate education placements of NE-LSAMP students.
Using our common commitment to LSAMP as a lynchpin, we have established
working relationships for project planning, information sharing, database management,
and budgetary operations during Phase I . We document our substantial progress
toward achieving the stated Phase I enrollment and degree completion objectives.
URM STEM majors increased by 12% in Year 3 and STEM bachelors degrees awarded
to URM students increased by 50% that year. We are on a trajectory to significantly
increase each measure by the final year of Phase I funding.
To our ongoing Phase I objectives we now add specific Phase II objectives: to
form an Alliance-wide community of LSAMP students through annual meetings and
inter-campus activities; to provide irnear peerlr graduate student mentors for LSAMP
students from NE-AGEP partners; to track individual LSAMP student persistence and
graduation and identify individual graduate STEM enrollment or professional STEM
placement. Alliance partners will track students in a database consistent with NSF
reporting requirements including all data elements that are submitted to QRC (the
LSAMP national reporting database). Along with students demographic and ethnic data,
the database will include sections for research accomplishments and post-baccalaureate
career path whether academic or professional employment.
The NE-LSAMP will continue its successful Phase I activities. Additionally, in
Phase II we will:
Implement an Alliance-wide UROP program as an outcome of our iubest
practicesli analysis at Advisory Board meetings. Faculty involvement with LSAMP
students is a required component of the undergraduate research opportunities now present
at each alliance campus and inter-campus interactions for UROP students will be added.
Partner with the NE-AGEP as a resource for graduate student itnear peerlr role
model mentors for our LSAMP students.
Convene a iostudent leadershipls conference for all URM STEM students each
spring to assist LSAMP students in career exploration and provide information about
applying to and financing graduate education.

The Northeast LSAMP (NELSAMP) has significantly increased underrepresented minority (URM) enrollment in STEM baccalaureate disciplines and their graduation at five independent institutions located in three different states. The Alliance enables its institutions to implement best practices that ensure student success, such as research opportunities and formal Supplemental Instruction programs. It also provides opportunities for NELSAMP students from the five institutions to interact and find a larger identity group through Alliance-wide events.
The proposed NELSAMP Senior Alliance aims to maintain and build upon its existing programs, develop intentional pathways for student progression from community college STEM associate degree programs into NELSAMP, and implement an NELSAMP-specific international research experience for upper level students. In addition, it will encourage other NELSAMP students to participate in existing international research activities by providing travel support funds.
The intellectual merit of the NELSAMP Senior Alliance is reflected in several aspects of its work. NELSAMP will develop a cohort model to track and support URM community college students through their combined AS-BS sequence in STEM majors. Near-peer activities and participation in Alliance-wide events will improve student persistence during their community college years. The international research components will, similarly, add to STEM persistence in the third and fourth undergraduate years.
The broader impacts of this proposed NELSAMP Senior Alliance include the increased pipeline of students from URM populations in three states who persist from high school ?directly or through community college -to degree completion in baccalaureate STEM disciplines. In addition to buttressing persistence in STEM for upper level NELSAMP students, the success of a dedicated international research experience program in South Africa ? a country with many institutions eager to partner with Alliances- should serve as a model to expand dramatically the number of international opportunities for other LSAMP students.