Janis Weeks

Professor, Department of Biology
Member, ION

Ph.D. University of California, San Diego
B.S. Massachusetts Institute of Technology

Upcoming Seminar: 4/7/2016

"Using high technology and electrophysiology to combat
ancient parasitic diseases"

jweeks@uoregon.edu
Office: 209 Huestis
Phone: 541-346-4517

 

Research Interests: Technology development for drug screening platforms, including anthelmintic (anti-nematode worm) drugs for human and animal health; nematode neurobiology and genetics; synaptic physiology; neural circuits for behavior; insect neurobiology; tropical infectious and parasitic diseases; research and education capacity building in Africa.

Overview: Traditionally, research in the Weeks lab investigated hormonal regulation of the structure, function and survival of neurons and neural circuits, using methods including electrophysiology, biophysics, genetics, genomics and behavioral analysis. This work focused on an extreme example of natural neural plasticity: insect metamorphosis in the moth, Manduca sexta, and fruit fly, Drosophila melanogaster, when neural circuits are reorganized to accommodate different life stages. Hormones similarly influence the vertebrate nervous system with relevance to human health such as Alzheimer's Disease and stress-induced cognitive decline.  

Since the mid-1990s, Weeks has increasingly been involved with research and education in Africa, and the study of tropical parasitic and infectious diseases. Infection with parasitic nematodes causes chronic, debilitating disease in humans and animals in many resource-limited regions of the world. Existing anthelmintic (anti-nematode) drugs are losing potency due to increasing drug resistance in the parasites, and new drugs are critically needed. Within this context, the Weeks lab turned its focus to the small roundworm, Caenorhabditis elegans, a powerful model organism for biological inquiry. The Weeks lab is using combined microfluidic and electrophysiological platforms developed with Shawn Lockery to accelerate the screening process for new anthelmintic drugs, using C. elegans. The ScreenChip platform is also useful for C. elegans models of human aging and disease. Recently, the Bill & Melinda Gates Foundation funded the successful modification of this technology for use with human parasites such as hookworm (Ancylostoma spp.) and roundworm (Ascaris). In 2011, Weeks and Lockery founded a UO spin-off company, NemaMetrix Inc., to enhance commercialization of these devices.

Weeks has taught in and organized advanced neuroscience courses throughout Africa (e.g., Senegal, Egypt, Kenya, Democratic Republic of Congo, South Africa, Ghana) for graduate and medical students, and neuroscience faculty, under the auspices of the International Brain Research Organization.  A member of the African Studies Program, Weeks performs healthcare fieldwork in Zimbabwe and is a student and performer of Zimbabwean music.  At UO, she teaches courses in global health [“Tropical Diseases in Africa” (Bi309) and “HIV/AIDS in Africa” (CHC434)] and helps direct a global-health-focused study abroad and internship program in Accra, Ghana, for undergraduates.  

RECENT PUBLICATIONS

Microfluidic platform for electrophysiological recordings from host-stage hookworm and Ascaris suum larvae: a new tool for anthelmintic research. Weeks JC, Roberts WM, Robinson KJ, Keaney M, Vermeire JJ, Urban Jr., JF, Lockery SR, Hawdon JM.. International Journal for Parasitology: Drugs and Drug Resistance, in press.

Microfluidic platform for electrophysiological recordings from host-stage hookworm and Ascaris suum larvae: A new tool for anthelmintic research.

Int J Parasitol Drugs Drug Resist. 2016 Sep 15;:

Authors: Weeks JC, Roberts WM, Robinson KJ, Keaney M, Vermeire JJ, Urban JF, Lockery SR, Hawdon JM

Abstract
The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device ('chip') that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels. Microfluidic technologies have transformed C. elegans research and the goal of the current study was to validate hookworm and Ascaris suum host-stage larvae in the microfluidic EPG platform. Ancylostoma ceylanicum and A. caninum infective L3s (iL3s) that had been activated in vitro generally produced erratic EPG activity under the conditions tested. In contrast, A. ceylanicum L4s recovered from hamsters exhibited robust, sustained EPG activity, consisting of three waveforms: (1) conventional pumps as seen in other nematodes; (2) rapid voltage deflections, associated with irregular contractions of the esophagus and openings of the esophogeal-intestinal valve (termed a 'flutter'); and (3) hybrid waveforms, which we classified as pumps. For data analysis, pumps and flutters were combined and termed EPG 'events.' EPG waveform identification and analysis were performed semi-automatically using custom-designed software. The neuromodulator serotonin (5-hydroxytryptamine; 5HT) increased EPG event frequency in A. ceylanicum L4s at an optimal concentration of 0.5 mM. The anthelmintic drug ivermectin (IVM) inhibited EPG activity in a concentration-dependent manner. EPGs from A. suum L3s recovered from pig lungs exhibited robust pharyngeal pumping in 1 mM 5HT, which was inhibited by IVM. These experiments validate the use of A. ceylanicum L4s and A. suum L3s with the microfluidic EPG platform, providing a new tool for screening anthelmintic candidates or investigating parasitic nematode feeding behavior.

PMID: 27751868 [PubMed - as supplied by publisher]