THE NOWICK RESEARCH GROUP

Research in the Nowick group involves the design, synthesis, and structural evaluation of molecules that are inspired by proteins. My students and I are developing unnatural building blocks that can be used alone or combined with natural amino acids to make synthetic molecules that mimic some of the structures and interactions of proteins. Students in my group learn state-of-the-art techniques for the synthesis of small molecules and peptides and also learn to study molecular structure, conformation, and interactions using modern spectroscopic, crystallographic, and molecular modeling methods.

 

Macrocyclic beta-sheet containing unnatural template and turn groups Hao (red) and delta-linked ornithine (blue).

We are especially interested in the structures and interactions of beta-sheets, which are important in Alzheimer's and other neurodegenerative diseases. By designing, synthesizing, and studying molecules that mimic the structures of supramolecular assemblies of peptides and proteins associated with these diseases, we are getting insights into the structures of the aggregates that may ultimately be critical to understanding and ultimately treating these devastating and intractable diseases.

 

X-ray crystallographic structures of a trimer (left) and a porelike assembly of peptides (right) associated with Alzheimer's disease.

Chemical synthesis, NMR spectroscopy, X-ray crystallography, and molecular modeling are our primary tools for asking how and why peptides and proteins interact and how we can manipulate these interactions. Our studies typically involve designing and synthesizing new molecules that we envision will interact through specific hydrogen-bonding, hydrophobic, and other non-covalent forces and then refining our understanding by studying their folding, supramolecular interactions, and biological properties. Being able to visualize at atomic resolution how the molecules fit together and how they interact with other molecules provides our laboratory with a unique window into diseases involving protein aggregation that may lead to the design of new drugs to treat Alzheimer's and other neurodegenerative diseases.

Students in the Nowick group partake fully of the rich environment of mentorship and training provided by our research laboratory. Graduate students participate in hypothesis generation, data collection, data analysis, and communication through oral and written presentation. I meet with students individually each Monday to discuss his or her results and plans for subsequent experiments. Additional scheduled and ad-hoc meetings occur throughout the week. When students are writing papers for publication, I work closely with them, providing guidance and feedback in the writing process. My group and I meet collectively on Tuesday evenings during our weekly group meetings. Our group meetings consist of three formats: research, literature, and workshop. In our research group meetings students present and discuss their results orally with slides and get feedback and discussion that leads to ideas for future experiments. In our literature group meetings we discuss important publications from the current literature, with each student making slide presentations on articles. In our workshop group meetings we focus on developing skills in topics such as organic reaction mechanisms, molecular modeling, and X-ray crystallography. Through this program of research training, continuing education, and mentorship, students acquire the skills to become successful independent scientists.