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E-mail: mia@molbio.mgh.harvard.edu
Web: http://xanadu.mgh.harvard.edu/avruchweb/maria/index.html
EDUCATION
Harvard University School of Medicine
Massachusetts General Hospital
Boston, MA 02114
Research Fellowship in Cancer Genetics - Dept. of Medicine
appointed to faculty September 1999.
Princeton University
Princeton, NJ 08544
Doctor of Philosophy degree in Molecular Biology awarded January 1999.
Princeton University
Princeton, NJ 08544
Master of Arts degree in Molecular Biology awarded June 1994.
Massachusetts Institute of Technology
Cambridge, MA 02139
Bachelor of Science degree in Biology awarded June 1992.
Grade Point Average: 4.4 out of 5.0
Stuyvesant High School
New York, NY 10009
High School Diploma awarded June 1988.
Grade Point Average: 95.45 %
PUBLICATIONS AND PRESENTATIONS
AWARDS AND HONORS
RESEARCH AND
TEACHING EXPERIENCE
Post-Doctoral Cancer Research: Identifying the functions of eukaryotic genes in
and related to the Ras pathway for oncogenesis using in vivo & in vitro techniques.
Identifying functions for signal transduction (S.T.) gene products involved in the
regulation of mitosis by protein phosphorylation.
Mentorship/teaching: Science in the Classroom/Timilty Middle School/Boston,Nov.2002-present
Designed and executed hands-on lessons on digestion and enzyme biochemistry for
80 6th graders; Consulted in curriculum design; Judged Science Fair;
more lessons/curriculum development planned and executed.
Masters Degree awarded in June 1994 for defense of a research proposal on
"Building a Collection of Novel DNA Binding Proteins". Research toward
the Ph.D. degree focused on understanding the primary determinants of
protein folding with the ultimate goal of designing proteins of specified
structures that have clinically therapeutic benefits. Doctoral Dissertation
completed Jan. 15, 1999 is entitled Rational Combinatorial Design Suggests
an Evolutionary Approach for Building Proteins.
Concurrent (June 1997-Jan.1999) with pursuit of PhD, I was Lab manager
of day-to-day operations.
Deletion analysis of DivL cellular differentiation gene of bacterium
Caulobacter crescentus.
Studied the patterned expression of the alkaline phosphatase enzymeTeaching & Research Assistantship in Core Lab course at Princeton U., Jan.1999-May 1999
(thought to be involved in cell adhesion) in the early stages of Drosophila
embryogenesis.
Assisted Dr. Alison Gammie with an extensive semester-long advanced course
in the practice and techniques of molecular biology research. Prepared reagents
and maintained laboratory for 80 students and assisted in the planning, grade
distribution, and administration of the course. Techniques covered in the course
included routine DNA preparation, cloning and sequencing. Methods in yeast
genetics and protein analysis were applied to the genetic analysis of mismatch
repair genes in the yeast S. cerevisiae that are implicated in colon cancer in humans.
Trained graduate student in expression and purification of protein library
candidates and charged her with mentoring an undergraduate; trained
undergraduate student in molecular cloning techniques involved in PCR-based
mutagenesis and orchestrated research plan for the completion of his
Bachelors thesis in Chemistry at Princeton U.; trained undergraduate in
phage library screening techniques, routine microbiology, transformation of
E. coli, protein purification and expression, Western Blotting, and approaches
for man-made protein library design: supervised in-depth the writing of her
Junior Research Paper (May 1998) and of her senior thesis (May 1999).
Taught basic macromolecular structure (nucleic acids and proteins),
acid-base biochemistry, carbohydrate, lipid and protein metabolism;
tutored individually and graded exams.
Taught basic molecular biology principles in class and one-to-one;
ran structured lab exercises on bacterial growth, DNA work, and
developmental biology; graded exams and lab reports.
Taught algebra, geometry and basic math in class and after hours;
proofread, corrected and wrote exams. All of my students successfully
entered Stuyvesant H. S. after entrance exams.
FURTHER RESEARCH,
WORK EXPERIENCE AND
PUBLIC SERVICE
Used RNA transcript analysis in an attempt to understand the genetic
structures of three alleles of a Drosophila melanogaster cell division
cycle mutation called rough deal (rod).
Undergraduate research under Drs. H. Steller & D. Rio, Drosophila
Project Lab, MIT, 1991
Searched the Drosophila genome on the molecular level for the coding
region of a protein called pleiotrophin, known to be critical for cell
division and nerve cell outgrowth in mammals.
Helped to characterize a Drosophila cell division cycle mutation called
spaghetti-squash (sqh), known to inhibit cytokinesis, as a leaky allele
on both the molecular and cytological levels. Work acknowledged in
Cell, v. 65: pp. 1177-1189, by R.E. Karess et al., 1991.
Helped to screen for alleles of a developmental maternal effect mutation
in Drosophila; helped to determine the effects of various genetic
deficiencies on Drosophila embryos.
Studied the effects of the mutagen methyl methane sulfonate on the
growth of and pigment production in the cyanobacterium
Microcystis aeruginosa.
(see Research and Teaching Experience).
Published articles, proofread submissions, designed layout,
and raised funds for publication
Service Volunteer at the Queensborough Public Library, summers 1985 and
1986
Junior Camp Counselor at the Manhattan Children's Museum, summer 1984
Ph.D. Thesis TITLE:
Rational Combinatorial Design Suggests An Evolutionary Approach for Building Proteins
Thesis Examination Details:
Name of Doctoral Degree Recipient: Maria Nicole Nedwidek
Name of Institution: Princeton University; Princeton, New Jersey
Name of Faculty Advisor: Dr. Michael H. Hecht
Name of Program Director and Primary Examiner: Dr. Thomas J. Silhavy
Remainder of Examining Committee: Dr. Clarence Schutt; Dr. Michael Cole
Thesis ABSTRACT:
This thesis explores the success of a rational library design approach called binary patterning that places hydrophobic amino acids at the core of a globular protein fold and hydrophilic amino acids at its exterior by establishing a particular periodicity of residues in the linear protein sequence. A library of 5 X 108 protein candidates patterned in this manner and designed to fold into three-helix bundles were displayed on bacteriophage and probed for their ability to form a discontinuous epitope that binds human Immunoglobulin G (IgG). The formation of this epitope was the measure of success for the design strategy. Of 2,000 and ultimately 100 selected candidates that were exhaustively screened, no true IgG-binders were found. The most salient explanation for this result is that the design strategy was not sufficient to achieve the desired fold in any measurable abundance by the methods employed. Design tactics that maintain the hydrophobicity of the protein core but also incorporate steric constraints and packing and would very likely produce a higher success rate are discussed. The ultimate purpose of this document is to understand what elements of rational design are necessary to achieve success at reproducibly designing particular and precise protein structures.
REFERENCES