My educational interests are microbiology, infectious disease, and global rural health.
The focus of our molecular parasitology laboratory is trypanosomes. These vector-borne protozoan parasites cause World Health Organization-designated Neglected Tropical Diseases that are endemic to poor, rural populations and for which new drug targets are urgently needed. The laboratory studies the stability and degradation of RNA, an important control point of trypanosome gene expression as transcription of both mitochondrial and nuclear genomes is constitutive in these organisms.
- Lab Updates
Trypanosomes Cause Human Diseases
The trypanosome subspecies Trypanosoma brucei brucei, infective to cattle, is non-infectious to humans and has become our most utilized trypanosome model system. Molecular parasitologists generally find this genetically malleable trypanosome convenient for exploring basic facets of trypanosome molecular biology and biochemistry. This is one of the two trypanosome species we use in our lab. Other T. brucei subspecies, T. brucei rhodesiense and gambiense are the causative agents of African Sleeping Sickness endemic to parts of Africa.
Trypanosoma cruzi is the other trypanosome species we study in the lab, and it causes Chagas’ disease, recently reviewed in the New England Journal of Medicine. Heart disease is a common outcome of chronic T. cruzi infection, which is endemic to South and Central America and is also a U.S. concern for our immigrant community. In fact, in December 2015 NPR reported on the U.S. impacts of this disease. T. cruzi has a very different life cycle than T. brucei and for this reason there are topics we specifically want to study in T. cruzi rather than T. brucei. We study multiple strains of T. cruzi which show differences in degree of infectivity and disease progression.
Trypanosomes: Masters at Reinventing Themselves
Many parasitic human pathogens are vector transmitted including T. cruzi, T. brucei, and the closely related Leishmania spp. T. cruzi is transmitted by the “kissing bug” and T. brucei by the tsetse fly. The environments of the human and insect hosts differ in temperature, pH, immune defenses, osmolarity, and nutrient availability. Therefore, trypanosomes transition through different life stages at which they are adapted to cope with the unique conditions of that stage (diagrams adjacent and below). Often the same trypanosome species in different life stages appears morphologically very different, and metabolism differs to cope the nutrient availability of the environment. We study the trypanosome gene expression changes that are necessary for survival at different life stages.
Trypanosome Mitochondrial Gene Expression is Stage-specifically Regulated and Very Different from that of Other Eukaryotes
Changing metabolic pathways due to changing nutrient accessibility make it likely that changes in metabolic gene expression occur throughout trypanosome life cycles. Many genes of the trypanosome mitochondrial genome encode components of the Electron Transport Chain, and others are required to sustain this important organelle, so much of our work focuses on its gene expression. RNA stability and a unique type of RNA editing are two control points for regulating abundance of mitochondrial gene products.
One focus of the lab is to understand how and why mitochondrial gene expression changes in T. cruzi as it progresses through its life cycle. We use cell culture, trypanosome cell biology techniques, quantitative RT-PCR, next-generation sequencing, and microscopy to test our hypotheses.
One focus is to better understand the role that a mitochondrial mRNA cis-acting element, 3’ non-encoded tails, plays in all aspects of mitochondrial gene expression. We work in T. brucei and use and both standard molecular techniques and next-generation sequencing approaches to answering these questions.
A third focus is to understand the biochemistry and function of the enzymes that degrade RNA – ribonucleases. We are currently characterizing a cytosolic ribonuclease. We have biochemically characterized its in vitro activity, and are now determining its localization and identifying potential substrates.
Recent Zimmer Lab Updates
April 18, 2019: Undergraduate Sean Faacks presents his poster "Regulatory elements' effect on gene expression in Trypanosoma brucei" at the UMD Undergraduate Research & Artistic Showcase.
April 1, 2019: Congratulations to Emily Susa for a successful Masters thesis defense entitled "Gene expression within the fluctuating life cycle stages of Trypanosome parasites".
March 29, 2019: Congratulations to undergraduate Alyssa Schuett, who was awarded a UROP Fellowship for Fall 2019 for her proposed project determining the activity of the putative trypanosome KPAP2 poly(A) polymerase.
March 19, 2019: Emily Susa presents a campus-wide general-audience Grad Talk entitled "Trypanosoma cruzi parasite, master of self-reinvention"
November 19, 2018: Congratulations to undergraduate Sean Faacks, who was awarded a UROP Fellowship for Spring 2019 for his proposed project about RNA binding protein domains in T. brucei.
October 26, 2018: PhD candidate Clara Smoniewski presents her poster on trypanosome mitochondrial poly(A) polymerases and their activities at the Rustbelt RNA Meeting in Columbus, OH.
June 18, 2018: Dr. Roger Ramirez-Barrios is awarded a 2018 Para Tryp travel fellowship to present a talk at the American Association of Veterinary Parasitologists 63rd Annual Meeting in Denver, CO in July.
May 14, 2018: Master of Science candidate Charles Liggett will give his public thesis seminar entitled "Powerhouse in Flux: Changes in Mitochondrial RNA Proessing During Starvation in Trypanosoma cruzi". 3PM, Room 130, School of Medicine.
April 27, 2018: The Zimmer laboratory is well-represented in the Integrated Biosciences Art Show. Thank you Emily and Clara for contributing.
January 10, 2018: The Zimmer laboratory is grateful for a grant from the NIH-National Institute of Allergy and Infectious Diseases awarded to Dr. Sara Zimmer for investigation of post-transcriptional nucleotide addition on trypanosomatid mitochondrial mRNAs.
Name: Sara L. Zimmer, PhD
Principle Investigator, Assistant Professor
Title: Principal Investigator
Department of Biomedical Sciences
1035 University Drive
Duluth, MN 55812-3031