ABOUT US

Our lab focuses on two topics. (1) Therapeutic protein engineering for improve pain control; (2) Genetics of microbial extremophiles, primarily hyperthermophiles including members of the archaeal and bacterial domains. We use archaea, bacteria, fungi and algae as platforms for genetic engineering to create new traits and to ask basic questions.  Our research is strongly interdisciplinary merging biology with chemistry, engineering with geology. Field work at geothermal sites provides another research component. The research outcomes provide solutions to societal needs including renewable energy, sustainable mining, vaccines and RNA chemistry. The main approach used in our lab is a functional genomics approach based on the creation and application of genetics systems coupled with bioinformatics. While molecular biology methods are a mainstay, additional efforts include the use of bioreactors, protein purification and metabolomics.

atoms

The organisms we study are Sulfolobus solfataricus and related species, which are thermoacidophilic organisms belonging to the Archaea. Metallosphaera sedula another archaeon, is the focus of studies on biotransformations of metal again at temperature extremes. Finally the thermophilic anaerobic bacteria, Thermotoga maritima, is the focus of studies on hydrogen metabolism.

Our lab focuses on two topics. (1) Therapeutic protein engineering for improve pain control; (2) Genetics of microbial extremophiles, primarily hyperthermophiles including members of the archaeal and bacterial domains. We use archaea, bacteria, fungi and algae as platforms for genetic engineering to create new traits and to ask basic questions.  Our research is strongly interdisciplinary merging biology with chemistry, engineering with geology. Field work at geothermal sites provides another research component. The research outcomes provide solutions to societal needs including renewable energy, sustainable mining, vaccines and RNA chemistry. The main approach used in our lab is a functional genomics approach based on the creation and application of genetics systems coupled with bioinformatics. While molecular biology methods are a mainstay, additional efforts include the use of bioreactors, protein purification and metabolomics.

atoms

The organisms we study are Sulfolobus solfataricus and related species, which are thermoacidophilic organisms belonging to the Archaea. Metallosphaera sedula another archaeon, is the focus of studies on biotransformations of metal again at temperature extremes. Finally the thermophilic anaerobic bacteria, Thermotoga maritima, is the focus of studies on hydrogen metabolism.

CHROMATIN MODIFICATION IN ARCHAEA AND ITS ROLE IN GENE EXPRESSION –NSF

Native archaeal chromatin proteins from Sulfolobus species are methylated and acetylate and they encode the enzymes necessary for protein modification. However, the inter-relatedness of chromatin protein modification and gene expression in archaeal cellular systems has not been examined. Three independent evolved cell lines with a 100-fold increase in acid resistance were obtained through adaptive laboratory evolution and these show shared patterns of chromatin modification and gene expression both are altered relative to controls. Based on genome resequencing, these alterations did not arise by mutation. Since altered chromatin modification and gene expression are heritable traits, some other mechanism must be responsible.

BIOHYDROGENESIS IN THE THERMOTOGALES — DOE BER

The production and consumption of molecular hydrogen drives the physiology and bioenergetics of many microorganisms in hydrothermal environments. As such, the potential of these microorganisms as model systems to probe fundamental issues related to biohydrogen production merits consideration. Specifically, it is important to understand how carbon/energy sources relate to the disposition of reducing power and, ultimately, the formation of molecular hydrogen by high temperature microorganisms. This project will focus on bacteria of the thermophilic order Thermotogales, fermentative anaerobes that produce H2 from simple and complex carbohydrates. A combination of metabolomics, genomics and genetics will be used to interrogate the Thermotoga system to expand understanding of biohydrogenesis.

BIOLEACHING IN METALLOSPHAERA SEDULA -ASFOR

Metallosphaera sedula is an organism capable of lithoautotrophic growth that is used for biomining of low-grade  ores. This project aims to improve the bioleaching capacity of this organism and gain a better understanding of unique archaeal lithoautrophy pathways through a combination of adaptive laboratory evolution and genetic engineering.

BIOMEDICAL: BIOMOLECULAR CHARACTERIZATION OF THERAPEUTIC EXOTOXINS FROM MAMMALIAN HOSTS: UNL BIOMEDICAL RESEARCH SEED GRANT

The limited number of therapeutic exotoxins approved by the FDA suffer from structural limitations, drastically reducing their therapeutic value. This problem arises from an inability to produce versions of these proteins exhibiting humanized glycosylation patterns, resulting in a short molecular half-life and insufficient interaction with the target site during treatment. Production of glycosylated exotoxins is difficult because conventional production platforms designed to produce glycosylated proteins are susceptible to the toxicity of the exotoxins themselves. To overcome these limitations, cell lines were developed that are exotoxin resistant and produce glycosylated versions of these proteins. Also, cell lines were programmed to secrete the potentially therapeutic exotoxins into the growth media. These results will stimulate adoption of natively glycosylated therapeutic proteins across cancer treatment and other diseases.

BACTERIAL TOXIN PROTEIN ENGINEERING –  DTRA

Many biological toxins are known to attack specific cell types, delivering their enzymatic payloads to the cytosol. This process can be manipulated by molecular engineering of chimeric toxins. The Clostridium botulinum C2 binding/translocation domain was retargeted to neural cell populations by deleting its non-specific binding domain and replacing it with a C. botulinum neurotoxin binding domain. This retargeted toxin may enable delivery of therapeutics to peripheral neurons and be of use in addressing experimental questions about neural physiology.

PUBLICATIONS

RECENT PUBLICATIONS

Pavlik, B.J., E. Hruska, K.E. Van Cott and P. Blum. 2016. Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol. Scientific Reports 6:23707
Blum, P., D. Rudrappa, R. Singh, S. McCarthy and B. Pavlik. 2016. Experimental Microbial Evolution of Extremophiles. In P.H. Rampelotto (ed.) Biotechnology of Extremophiles: Advances and Challenges.
McCarthy, S., T. Johnson, B. Pavlik, S. Payne, W. Schackwitz, J. Martin, A. Lipzen and P. Blum. 2015. Expanding the Limits of Thermoacidophily in the Archaeon Sulfolobus solfataricus by Adaptive Evolution. Applied and Environmental Microbiology 82(3): 857-67.
Rudrappa, D., A. Yao, D. White, B.J. Pavlik, R. Singh, M.T. Facciotti and P. Blum. 2015. Identification of an archaeal mercury regulon by chromatin immunoprecipitation. Microbiology, 161:2423-33
McCarthy, S., C. Ai, G. Wheaton, R. Tevatia, V. Eckrich, R. Kelly and P. Blum. 2014. Role of an archaeal PitA transporter in the copper and arsenic resistance of Metallosphaera sedula, an extreme thermoacidophile. Journal of Bacteriology 196(20):3562-70.
Schelert, J., D. Rudrappa, T. Johnson and P. Blum. 2013. Role of MerH in Mercury Resistance in Sulfolobus solfataricus.Microbiology 159:1198-208.
Maezato, Y., T. Johnson, S. McCarthy, K. Dana and P. Blum. 2012. Metal Resistance and Lithoautotrophy in the Extreme Thermoacidophile Metallosphaera sedula.Journal of Bacteriology 194(24):6856-6863.

RECENT PUBLICATIONS

Pavlik, B.J., E. Hruska, K.E. Van Cott and P. Blum. 2016. Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol. Scientific Reports 6:23707
Blum, P., D. Rudrappa, R. Singh, S. McCarthy and B. Pavlik. 2016. Experimental Microbial Evolution of Extremophiles. In P.H. Rampelotto (ed.) Biotechnology of Extremophiles: Advances and Challenges.
McCarthy, S., T. Johnson, B. Pavlik, S. Payne, W. Schackwitz, J. Martin, A. Lipzen and P. Blum. 2015. Expanding the Limits of Thermoacidophily in the Archaeon Sulfolobus solfataricus by Adaptive Evolution. Applied and Environmental Microbiology 82(3): 857-67.
Rudrappa, D., A. Yao, D. White, B.J. Pavlik, R. Singh, M.T. Facciotti and P. Blum. 2015. Identification of an archaeal mercury regulon by chromatin immunoprecipitation. Microbiology, 161:2423-33
McCarthy, S., C. Ai, G. Wheaton, R. Tevatia, V. Eckrich, R. Kelly and P. Blum. 2014. Role of an archaeal PitA transporter in the copper and arsenic resistance of Metallosphaera sedula, an extreme thermoacidophile. Journal of Bacteriology 196(20):3562-70.
Schelert, J., D. Rudrappa, T. Johnson and P. Blum. 2013. Role of MerH in Mercury Resistance in Sulfolobus solfataricus.Microbiology 159:1198-208.
Maezato, Y., T. Johnson, S. McCarthy, K. Dana and P. Blum. 2012. Metal Resistance and Lithoautotrophy in the Extreme Thermoacidophile Metallosphaera sedula.Journal of Bacteriology 194(24):6856-6863.

EDUCATION

The Blum lab participates in multiple educational and outreach activities for undergraduates and high school students.

EDUCATION

The Blum lab participates in multiple educational and outreach activities for undergraduates and high school students.

dna

CURRENT LAB MEMBERS

paul

Dr. Paul Blum

(P.I.)
deepak

Dr. Deepak Rudrappa

(Research Assistant Professor)
derrick

Derrick White

(Doctoral)
ben

Benjamin Pavlik

(Doctoral)
tyler

Tyler Johnson

(Doctoral)
samuel

Samuel McCarthy

(Doctoral)
sophie

Sophie Payne

(Doctoral)
erorn

Erin Oeltjen

(Undergraduate)
erica

Erica North

(Undergraduate)

PREVIOUS LAB MEMBERS

Elizabeth Hruska (Undergraduate), Raghuveer Singh (Ph.D. ‘16), Collin Mach (Undergraduate), Aubrey Mueller (Undergraduate), Abdul Tahlil (NSF, Undergraduate) Erica Keffeler (NSF, Undergraduate), Chenbing Ai (Visiting student), Yuting Liang (Visiting student), Bree Drda (Undergraduate), Connie Chen (NSF, Undergraduate) Danielle Pascoli (Undergraduate), Rahul Tevatia (Ph.D. '14) , Valerie Eckrich (Undergraduate), Laura Freese (Undergraduate), Mary Walter (Undergraduate, Technical) Levi Kramer (NSF, Undergraduate), Sreedevi Madhusoodhanan (Ph.D. ‘13), Landon Peterson (Undergraduate, Technical), Karl Dana (Technical) , Yukari Maezato (Ph.D. '12) Benjamin Bira (NSF, Undergraduate), Karla Piedl (NSF, Undergraduate), Katie Starostka (Technical)

CONTACT US

CONTACT US

ADDRESS

1901 Vine St.

Lincoln, NE 68588

EMAIL

blumlab@blumlab.org


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