IFER funds new graduate fellowships for research into the development of alternatives to the use of animals in science

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In the Spotlight

IFER funds new graduate fellowships for research into the development of alternatives to the use of animals in science

by Sherry Ward, AltTox Contributing Editor and member of IFER Scientific Advisory Board

Posted: October 15, 2014

Peggy Cunniff, President of the International Foundation for Ethical Research (IFER), and Peter O’Donovan, Executive Director of IFER, announced this week the funding of three new graduate fellowships, and the renewal of three fellowships awarded in previous years. The awards are based on recommendations of the IFER Scientific Advisory Board following their review of applicant proposals at the September 8 annual meeting, and approval by the IFER Board of Directors.

Each of the IFER awards supports the development of an innovative non-animal methodology with the potential to replace the use of animals in an area of biomedical research or safety testing.

The three 2014 fellowship awardees, and their areas of research, are the following:

(1) Human Cancer-on-a-Chip as a replacement for animal testing
Graduate Student: Bryan Hassell
Faculty Advisor: Dr. Donald E. Ingber
Educational Institution: Wyss Institute for Biologically Inspired Engineering, Harvard University

An exciting application of microfluidic devices is their use to create “organs-on-chips” based on recreating the microenvironment, cellular structures, and functions of a human tissue or organ. These human-cell based devices can then be used in various laboratory protocols, such as in vitro models for drug development, toxicity testing, and research models for human diseases. Such models have the potential to reduce and even replace animal models.

The laboratory of Dr. Ingber has developed various microfluidic models of human organs, including a human “lung-on-a-chip.” This model recreates the lung’s mechanical microenvironment of breathing and vascular flow, as well as the ability to integrate and study various types of cell-cell interactions. Lung-on-a-chip devices can be created using primary human cells, induced pluripotent stem cells (iPSC), or patient-derived cells.

The objective of Bryan Hassell’s proposal “is to develop Organ-on-a-Chip microfluidic devices that recreate the microenvironments of both primary and metastatic lung cancer lesions, with the goal of replacing animal lung tumor models for identification of new anticancer therapies.”

Lung-on-a-chip schematic
Schematic of Lung-on-a-Chip. (Source: Laboratory of D.E. Ingber)

(2) Structural and functional neuroplasticity of Parkinson’s disease following a sensori-motor contingent musical walking intervention (Ambulosono)
Graduate Student: Sun Nee Tan
Faculty Advisor: Dr. Martin McKeown
Educational Institution: University of British Columbia, Vancouver, Canada

This study will investigate the mechanisms of action of a music-contingent walking exercise program called Ambulosono in Parkinson’s disease (PD) subjects. Stride length in PD subjects is assessed with sensors, and music abruptly stops when the stride length is not sufficient. Preliminary results indicate improvements in gait and cognition in PD, however, the mechanisms of improvement are unclear.

This project will tease apart the potential mechanism(s) using non-invasive testing on humans to look at both structural and functional connections in the brain and their relationships with clinical data. The MRI technique of myelin water imaging (MWI) will be used as a biomarker for myelin. Exploring the relationship between structural and functional connectivity alterations is expected to improve understanding of the pathophysiology of PD. Tan cited previous studies demonstrating the potential to link microscopic changes to non-invasive imaging modalities suitable for humans (i.e., MRI) (Zatorre et al., 2012; Prasloski et al., 2012). Historically, neuroscience studies investigating synaptic plasticity have required the sacrifice of many animals to understand the underlying cellular and molecular mechanisms of learning abilities.

Results will also provide objective measures of the effectiveness of the music-contingent exercise program to slow disease progression. Moreover, biomarkers/connectivity parameters developed in this study to quantify neuroplasticity in PD have potential applicability to other neurological disease research to validate the effectiveness of interventions without the sacrifice of animals. Considering the large amount of new funding for brain research through the US Brain Initiative program, the IFER SAB saw the potential development and validation of non-invasive human research methods, like those proposed in this study, as a high priority.

histogram
Histogram of myelin water fraction (MWF) values across all voxels (red line) from single Parkinson’s disease subject with “normal” appearing white matter on standard MRI compared to historic norms generated from 42 healthy subjects (shaded area). This study will determine whether interventions that improve symptoms, and possibly modify the disease, also have an effect of shifting the MWF values toward normality. (Source: Laboratory of M. McKeown)

(3) In vitro 3D flow through system for improved intestinal permeability model
Graduate Student: Erica Schlesinger
Faculty Advisor: Dr. Tejal Desai
Educational Institution: University of California San Francisco

An in vitro model commonly used to estimate intestinal absorption of orally ingested drugs is a simple 2-dimensional model of Caco-2 cells on a permeable membrane. This model, however, does not replicate the complex cellular and 3-dimensional (3D) structure of the intestine, which is a flow-through system lined with epithelial cells on 3D finger-like projections called micro-villi.

Schlesinger explains that Caco-2 cells have been shown to differentiate and adopt various regional functionalities seen in the in vivo intestinal epithelium when grown in more physiologically-relevant environments. The goal of the proposed research is to improve the in vitro intestinal absorption model so that it more accurately represents the intestine and its microenvironment.

The proposed research involves creating an in vitro tubular-shaped, flow-through model where the Caco-2 cells will be maintained on a surface made up of villi-like micro-structures as a more representative model of the intestinal wall. The Desai lab has already developed processes for creating microscale polymer structures for use in tissue engineering, and found that, at least with osteoblast cells, that “topography can be a more important determinant of the cell/surface interaction than the surface chemistry and/or stiffness.” In the proposed model of intestinal absorption, a drug will be introduced into the representative lumen flow and the amount penetrating through the cells will be measured.

The researchers “hypothesize that the presence of these villi structures combined with the dynamic flow will create a more relevant environment that causes the cells to more closely represent those found in real intestines. Such a system has the potential to not only improve bench-top evaluation of drug absorption and delivery, reducing the need for more complex animal studies, but could also be valuable in evaluating intestinal disease.”

fabrication process diagram
Fabrication process for villi-like micro-features on a porous film. (Source: Laboratory of T. Desai)

Fellowship Renewals

IFER graduate fellowships were renewed for an additional year for the three students listed below. The proposed research of these students is described in the 2013 IFER news announcement.

(1) In vitro prediction of skeletal teratogenicity of environmental chemicals
Graduate Student: Nicole Sparks
Faculty Advisor: Dr. Nicole I. zur Nieden
Educational Institution: University of California, Riverside

(2) Identification of pathways of developmental neurotoxicity (DNT) of environmental chemicals by -omics technologies
Graduate Student: Georgina Harris
Faculty Advisors: Dr. Lena Smirnova and Dr. Thomas Hartung
Educational Institution: Center for Alternatives to Animal Testing, Johns Hopkins University

(3) Development of a patient-specific high-throughput cardiac drug-screening platform
Graduate Student: David Tran
Faculty Advisor: Dr. Steven George
Educational Institution: University of California, Irvine

IFER Graduate Fellowships:

IFER, founded in 1985 and headquartered in Chicago, Illinois, is supported primarily by a grant from the National Anti-Vivisection Society (NAVS). One of the methods IFER uses to fulfill its mission “to support the development, validation, and implementation of scientifically valid methodologies that advance scientific research, product testing, and education without harming animals” is the award of fellowships to graduate students to support the development and/or incorporation of innovative animal alternative methods into their studies.

IFER Graduate Fellowships provide up to $15,000 per awardee per year for up to 3 years. A limited number of full proposals are invited each year from among the open call for pre-proposals, which are submitted annually on March 31. For information on eligibility, areas of interest, guidelines, and past award recipients, visit the IFER website, or contact Mr. Peter O’Donovan at ifer@navs.org.

Organizations and individuals interested in donating or sponsoring an IFER fellowship, or other type of animal alternative research project, should also contact Mr. O’Donovan.