Category Archives: News

Chemistry Professor Gives Women in STEM a Step Up

Pushpalatha Murthy (left) and Rohini Godbole at a STEM professional women's workshop in Bangalore.

Women may be an underrepresented group in the STEM fields (Science, Technology, Engineering and Math) at Michigan Tech, but Pushpalatha (Pushpa) Murthy is doing something about it—not only at Tech, but nationally and internationally.  A professor of chemistry at Michigan Tech, she is currently working at the National Science Foundation (NSF) as program director in the Division of Graduate Education.  She has been involved with the Graduate Research Fellowship Program (GRFP) and the NSF Research Traineeship (NRT) program.  She is also in charge of GRFP outreach activities to historically black colleges and universities.

Murthy recently worked with women in STEM in India. “I’ve always been interested in underrepresented groups in the STEM field,” states Murthy. In India, she focused on faculty and their professional development.

Traveling to both New Delhi in the north of India and Bangalore in southern India, Murthy and other leaders ran workshops for women in STEM, including programs like Career Launch and Acceleration, Factors that Impact Women’s Careers and The Art of Effective Negotiation. Murthy says the women faculty members were motivated and excited to participate in these workshops, as this was the first time they were attending workshops focused on their own advancement.  

“Most of the research on this topic has been conducted in the United States,” she explains. “Most other countries do not have research data on issues women in STEM or other careers face.   International women are very interested in the subject and want to know how the data apply to their situation.”  

Her passion for helping other women develop professionally started at Michigan Tech, where Murthy won the Distinguished Faculty Service Award and continued with her involvement in COACh (Committee on the Advancement of Women Chemists.) COACh has been growing its efforts for women scientists and engineers in the US and developing countries through a series of in-country career workshops and networking events.

Murthy is back in the US, but her passion for helping all underrepresented groups in their career development continues. “I’m interested in women in STEM across the globe and especially in the United States and India, because I’m from India and came here for my graduate studies,” she says. “It was been very exciting for me.  I want to share the research data and my experiences with others so they will have more opportunities.”

 

 

 

Chemistry Alumni Stephen F. Hahn 2014 College of Sciences and Arts Academy inductee

Stephen F. (Steve) Hahn is from Midland, MI and earned his BS in Chemistry from Michigan Technological University in 1982 and an MS in Chemistry from Central Michigan University in 1990. Steve joined The Dow Chemical Company in 1982 and has worked in a variety of research and new business development functions since that time. He currently heads Dow’s Ventures and Business Development group in the San Francisco/Silicon Valley area. He holds 41 issued U.S. patents and numerous international patents, and has authored 40 publications in refereed journals and 6 chapters in scientific reference books.

Steve was named Dow Inventor of the Year in 1990 and 1996, delivered the Distinguished Alumni Lecture at Michigan Tech in 1996 and 2003, and received the Dow Excellence In Science Award in 1999. He was a Visiting Professor of Chemistry and IPrime Scholar at the University of Minnesota in 2002. He received the American Chemical Society Cooperative Research Award in 2008 and the Council for Chemical Research Collaboration Award in 2010. Steve has represented Dow on several advisory boards including those at the University of Connecticut Institute for Materials Science and at Michigan Tech. He currently serves on the advisory board for the Global Social Venturing Competition at the Haas School of Business at UC-Berkeley and the Innovation Grant Committee at the Lawrence Berkeley National Laboratory.

From 2014 Induction to the College of Sciences and Arts Academy

 

 

 

Bio-Oligomer Purification, Electrophilic Oligo Synthesis, and Progress to a Genome Sequencer

CHEMISTRY SEMINAR

Michigan Technological University

Friday, December 12, 2014

3:00 pm Chemical Sciences Building Room 101

Dr. Shiyue Fang

Associate Professor, Chemistry Department

Abstract:

Bio-Oligomer Purification, Electrophilic Oligo Synthesis, and Progress to a Genome Sequencer

The progress on three projects, which are bio-oligomer purification, electrophilic oligosynthesis, and developing a new genome sequencer, will be presented. For bio-oligomer purification, we have developed two methods for oligodeoxynucleotide and one method for peptide purification. They are catching failure sequences by polymerization and catching full-length sequences by polymerization. Both methods do not require any type of chromatography,and purification is achieved through simple manipulations such as shaking and filtration. As aresult, they are suitable for large scale purification of drugs based on oligonucleotides and peptides. They are also ideal for small scale purification and high throughput purification. Currently, there are three oligonucleotide drugs and over 60 peptide drugs on the market, and many more are in various stages of clinical trials. Because known bio-oligomer purification methods such as HPLC have drawbacks such as high capital cost for instrument, labor-intensiveness and requirement of large volumes of harmful solvents, the new methods are expected to be preferred by pharmaceutical companies for drug purification, and by academic labs and biotech companies for small scale and high throughput purification. For electrophilic oligo synthesis, we have made progress on developing a new method that features using protecting groups and linkers cleavable under nearly neutral conditions. Under these conditions, electrophilic groups such as ester, thioester, alpha-halo carbonyl, epoxide and aziridine are stable. As a result, the new method is useful for the synthesis of oligonucleotide analogs that contain such  sensitive functionalities. Using known oligo synthesis methods, such analogs cannot be synthesized. The new oligo synthesis method is expected to open doors to many research projects that require  sensitive oligo analogs. For developing a new genome sequencer, we are using AFM to monitor the  conformational fluctuations of a DNA polymerase during DNA synthesis. Because different  nucleotides are expected to give different conformational fluctuations, DNA sequences can be read  out in real-time. We have made progress on mutating a polymerase and solving several potential  problems for assembling the sequencer.

NON-CHROMATOGRAPHIC PURIFICATION OF SYNTHETIC BIOOLIGOMERS

Durga Pokharel

Advisor: Dr. Shiyue Fang

Doctoral candidate, Department of Chemistry

PhD Defense

Friday December 12, 2014   9:30am     Fisher 130

 

NON-CHROMATOGRAPHIC PURIFICATION OF SYNTHETIC BIOOLIGOMERS

Abstract

 

Synthetic oligonucleotides and peptides have found wide applications in industry and academic research labs. There are ~60 peptide drugs on the market and over 500 under development. The global annual sale of peptide drugs in 2010 was estimated to be $13 billion. There are three oligonucleotide-based drugs on market; among them, the FDA newly approved Kynamro was predicted to have a $100 million annual sale. The annual sale of oligonucleotides to academic labs was estimated to be $700 million. Both bio-oligomers are mostly synthesized on automated synthesizers using solid phase synthesis technology, in which nucleoside or amino acid monomers are added sequentially until the desired full-length sequence is reached. The additions cannot be complete, which generates truncated undesired failure sequences. For almost all applications, these impurities must be removed. The most widely used method is HPLC. However, the method is slow, expensive, labor-intensive, not amendable for automation, difficult to scale up, and unsuitable for high throughput purification. It needs large capital investment, and consumes large volumes of harmful solvents. The purification costs are estimated to be more than 50% of total production costs. Other methods for bio-oligomer purification also have drawbacks, and are less favored than HPLC for most applications.

To overcome the problems of known biopolymer purification technologies, we have developed two non-chromatographic purification methods. They are (1) catching failure sequences by polymerization, and (2) catching full-length sequences by polymerization. In the first method, a polymerizable group is attached to the failure sequences of the bio-oligomers during automated synthesis; purification is achieved by simply polymerizing the failure sequences into an insoluble gel and extracting full-length sequences. In the second method, a polymerizable group is attached to the full-length sequences, which are then incorporated into a polymer; impurities are removed by washing, and pure product is cleaved from polymer. These methods do not need chromatography, and all drawbacks of HPLC no longer exist. Using them, purification is achieved by simple manipulations such as shaking and extraction. Therefore, they are suitable for large scale purification of oligonucleotide and peptide drugs, and also ideal for high throughput purification, which currently has a high demand for research projects involving total gene synthesis. The savings with the new techniques compared with HPLC are estimated to be 70% to 90% depending on purification scale and throughput. We expect these new oligonucleotide and peptide purification technologies to be widely used in academic research labs, biotechnology companies, and pharmaceutical companies in the near future.

Purification and Carbohydrate Binding Properties of Two New Plant Proteins

Mr. Robert K Brown

Advisor: Dr. Tarun K Dam

Master’s Candidate Department of Chemistry

Michigan Technological University

“Purification and Carbohydrate Binding Properties of Two New Plant Proteins”

 

Friday, December 12, 2014

10:00 – 11:00 AM 

Room 404 ~ Administration Building
Purification and Carbohydrate Binding Properties of Two New Plant Proteins

Abstract:

 

Protein glycosylation is an important post-translational modification for many biological processes such as cell recognition, intercellular communication and cell death. Proteins that are able to bind to glycosylated proteins via carbohydrates are called lectins. Hemolytic lectins are proteins or glycoproteins that undergo specific interactions with cell surface carbohydrates and subsequently induce cellular lysis. They are termed “hemo” lytic because of their ability to lyse erythrocytes. We have isolated a novel hemolytic lectin named HelyX from the bulbs of a monocot plant, as well as a mannose-binding lectin named DIL from a separate monocot species. HelyX is a uniquely robust hemolytic lectin. It shows concentration dependent reversible hemolytic/agglutinating properties against both human and rabbit erythrocytes. The activity was found to be carbohydrate dependent. HelyX was isolated using ammonium sulfate precipitation, size exclusion chromatography, and analyzed by gel electrophoresis. DIL was purified using a modified version of a newly developed protocol. DIL interacts with the plant enzyme invertase with high affinity. This high affinity interaction suggests that the binding site of DIL is complimentary to glycoproteins containing larger high mannose glycans. Invertase is central to plant metabolism and defense. Therefore DIL might play a modulatory role in plant metabolism and defense through its interaction with invertase. HelyX and DIL did not show lytic activity on free living amoeba, Acanthamoebae. Instead the lectins promoted cyst formation of amoeabae trophozoites indicating a lectin-mediated rearrangement of membrane architecture. This result indicates that the lytic activity of HelyX or DIL depends on the macromolecular landscape of the cell membrane.

Evolution of Selected Isoprene Oxidation Products in Dark Aqueous Ammonium Sulfate

MS Defense:  DM Ashraf Ul Habib
Chemistry Department

Lynn Mazzoleni, Advisor
Thursday, December 4  1pm,  Chem Sci 101
Evolution of Selected Isoprene Oxidation Products in Dark Aqueous Ammonium Sulfate

The climate of the world is changing but our understanding of atmospheric processes is limited. Atmospheric aerosol is a trace but very influential medium of the atmosphere. Especially little is known about the organic aerosol components and their aqueous phase chemical evolution. To address this, the aqueous phase processing of glyoxylic acid, py­ruvic acid, oxalic acid and methylglyoxal was studied simulating dark and radical free atmospheric aqueous aerosol. A novel observation of the cleavage of a carbon-carbon bond in pyruvic acid and glyoxylic acid leading to their decarboxylation was made in the presence of ammonium salts but decarboxylation was not observed from oxalic acid. The empirical rate constants for decarboxylation were determined and are competitive with nighttime OH radical reactions. The structure of the acid, ionic environment of the solu­tions and concentration of species were all found to affect the rate of decarboxylation. A tentative set of reaction mechanisms is proposed involving nucleophilic attack by ammo­nia on the carbonyl carbon leading to fragmentation of the carbon-carbon bond between the carbonyl and carboxyl carbons. Under similar conditions in atmospheric aerosol, the aqueous phase processing may markedly impact the physicochemical properties of aerosol.

 

Synthetic Oligodeoxynucleotide Purification via Catching by Polymerization

Suntara (Boat) Fueangfung

Advisor: Dr. Shiyue Fang

Doctoral candidate, Department of Chemistry

Michigan Technological University

Friday, December 5, 2014, 9:00 am

Admin Building, Room 404

PhD Defense

 

Synthetic Oligodeoxynucleotide Purification via Catching by Polymerization

Abstract

Large quantities of pure synthetic oligodeoxynucleotides (ODNs) are important for preclinical research, drug development, and biological studies. These ODNs are synthesized on an automated synthesizer. It is inevitable that the crude ODN product contains failure sequences which are not easily removed because they have the same properties as the full length ODNs. Current ODN purification methods such as polyacrylamide gel electrophoresis (PAGE), reversed-phase high performance liquid chromatography (RP HPLC), anion exchange HPLC, and affinity purification can remove those impurities. However, they are not suitable for large scale purification due to the expensive aspects associated with instrumentation, solvent demand, and high labor costs.

To solve these problems, two non-chromatographic ODN purification methods have been developed. In the first method, the full-length ODN was tagged with the phosphoramidite containing a methacrylamide group and a cleavable linker while the failure sequences were not. The full-length ODN was incorporated into a polymer through radical acrylamide polymerization whereas failure sequences and other impurities were removed by washing. Pure full-length ODN was obtained by cleaving it from the polymer. In the second method, the failure sequences were capped by a methacrylated phosphoramidite in each synthetic cycle. During purification, the failure sequences were separated from the full-length ODN by radical acrylamide polymerization. The full-length ODN was obtained via water extraction. For both methods, excellent purification yields were achieved and the purity of ODNs was very satisfactory. Thus, this new technology is expected to be beneficial for large scale ODN purification.

Proposals in Progress

PI Xiaohu Xia (Chem), “Facile Removal of Surface Ligands from Supported Platinum-Group Metallic Nanocrystals,” American Chemical Society

PI Loredana Valenzano (Chem), “Bringing New Efficiencies in Petroleum Refining Processes: A Quantum Chemical Investigation of Novel Porous Materials and Metal Oxide Surfaces for Olefin and Paraffin Separation,” American Chemical Society

PI Lanrong Bi (Chem/BRC), “Buckyballs-Based Mitochondrial Drug Delivery System for the Prevention and Treatment of Ischemia/Reperfusion Injury,” US Department of Health and Human Services, NIH

PI Marina Tanasova (Chem), “Discovering Probes to Overcome Cancer Resistence to DNA Alkylating Chemotherapy by High Throughput Evaluation of Polymerase Inhibition,” US Department of Health and Human Services, NIH

PI Lanrong Bi (Chem/BRC) and Co-PI Qinghui Chen (KIP/BRC), “Target Mitochondrial Fusion Process: Engineering of a Nanoparticals-Based Mitochondrial Drug Delivery Platform,” US Department of Health and Human Services-NIH

PI Martin Thompson (Chem), “Development of a Biological Platform to Study Histone Modifications,” NSF

PI Lynn Mazzoleni and Co-PI Marina Tanasova (Chem), “Collaborative Research: The Role of Inorganic Salts in Functionalization and Fragmentation of Isoprene Oxidation Product—A Molecular-Level Investigation,” NSF

PI Tarun Dam (Chem), “Role of Glycoconjugate Scaffolds in Lectin Recognition,” NSF

PI Haiying Liu and Co-PI Ashutosh Tiwari (Chem), ” BODIPY-Based Ratiometric Near-Infared Fluorescent Probes for Zinc(II) and Active Oxygen Species,” NSF

Proposals in Progress

Haiying Liu (Chem), “Point-of-Care Rapid Detection by Label Free Cell and Nucleic Acid Assays,” Oakland Univeristy

Lynn Mazzoleni (Chem), “Collaborative Research: Nitrogen Partitioning and Evolution of Particulate Organic Nitrogen in Peat Fire Emissions,” National Science Foundation

Rudy Luck (Chem), “SusChEM: Using Abundant First Row Transition Metals to Accomplish Cross-Coupling for the Synthesis of Specific Drugs,” National Science Foundation