Bedford Research Foundation 2011 Newsletter

Read about all of the progress and the research that has occurred at the Foundation over the course of the past year! Dr. Kiessling outlines her vision for the upcoming year as well. Thank you for your support.

Progress in Circadian Rhythms And Stem Cells

BSCRF’s new mouse embryonic stem cells, PL034 (see below for information on the first incubator videomicroscope).

BSCRF scientists have derived two unique lines of stem cells that may lead to a breakthrough in the efficiency of stem cell derivation and expansion.

BSCRF scientists are following up their discovery that the genes that regulate the rhythms of daily life, circadian rhythm genes, may play important roles in stem cell derivation and stability in culture. Circadian rhythm genes regulate cells in the body by turning “on” and “off” over a 24-hour cycle in response to signals such as light/dark cycles, hormone pulses, and body temperature variations.

Currently, stem cells are cultured in constant temperature in the dark. If BSCRF’s research
proves that circadian rhythm genes play important roles in stem cell division and stability, it could markedly improve the efficiency of stem cell derivation and expansion, urgently needed to produce major advances in stem cell therapy.

Circadian Rhythm Genes: turn “on” and “off” in response to the rhythm of daily life.

To conduct this research, foundation scientists are using a genetic technology that links the circadian genes of a mouse with a gene from a firefly. When the circadian gene is “on”, the mouse cells glow like a firefly; when the circadian gene is “off”, the cells go dark. This mouse, “PER2Luc,” was derived by a circadian gene scientist several years ago and has been used by Dr. Fred Davis of Northeastern University, to study circadian gene expression in mouse tissues.

Body temperature of the mouse dips approximately 1 celsius at the beginning and the end of daylight.

BSCRF scientists have derived two new lines of embryonic stem cells from PER2Luc embryos. Light emitted by the stem cells is detectable in Dr. Davis’s luminometer, but BSCRF scientists are developing microscope equipment to record light emitted by individual cells in order to compare standard stem cell culture conditions with new culture conditions that support circadian rhythm such as the temperature variations of a mouse. These new stem cells will also be useful to all scientists seeking to understand the relationship between circadian rhythm and cell functions.

If supporting circadian rhythm genes is important to stem cells, either for their expansion as pluripotent cells or for their uniform differentiation, new methods of stem cell culture need to be developed.

To begin to determine the importance of circadian genes, BSCRF scientists have brought together several different pieces of equipment in order to continually visualize the new PER2Luc stem cells and their emission of light. Because the bioluminescence signal is very low, special cameras are being tested to find one that can detect light emission in individual cells in culture.

The programmable microscope stage incubator (OkoLabs) is being quality controlled by monitoring the cleavage and development of fertilized mouse eggs continuously for six days because mouse embryos require extremely fastidious culture conditions for successful early development. This work has provided new benchmarks for early mouse embryo development in culture to the stages needed for successful stem cell derivation.

The PER2Luc mouse has circadian genes coupled with firefly “Luciferase” genes. When the circadian genes turn “on” they glow, dimly, like a firefly under the microscope.

The 2011 Activated Egg Symposium

2010 Keynote: Janet Rossant,  PhD

Nov 4, 2011: The keynote for our ninth annual symposium is Dr. Janet Rossant, Professor of Molecular Genetics, Obstetrics and Gynecology, University of Toronto, and Chief of Research at the Hospital for Sick Children.

Dr. Rossant is internationally recognized for her pioneering research on stem cells and how they develop into tissues. Dr Rossant will speak on “Manipulating the mouse embryo: from lineages to stem cells and back again.” (see full speaker list at the Symposium Website) The dinner speaker is Chris Hempel, Founder, Addi and Cassi Fund, with compelling talk on the “Regulatory hurdles to research”.

Sponsored by Hamilton Thorne, The McKnight Foundation, Irv & Diane Naylor and Qualcomm.

Testis Stem Cell Project

Thanks to private donations, BSCRF scientists have launched the testis stem cell project.

Phase 1 is the isolation of a new line of testis stem cells from the Per2Luc mouse to study the role of circadian genes in testis stem cells. Phase 2 is to improve the efficiency of deriving testis stem cells from cryopreserved (frozen to stay alive) Per2Luc testis tissues. Phases 1 and 2 are underway.

Phase 3, starting in early 2012, will be to collaborate with Dr. Martin Dym, Georgetown University, in deriving human testis stem cells from cryopreserved biopsies archived in his laboratory. We will compare the efficiency of testis stem cell derivation using our newly developed circadian culture conditions with the efficiency previously reported by Dr. Dym.

Phase 4 will derive patient-specific stem cells from the male volunteers for our study.

CWU Alumni Award

In October, Dr. Kiessling was honored by Central Washington University with the Distinguished Alumni Award. Dr. Kiessling earned her second Bachelor’s and a Master’s degree there. Robert Lowery of CWU praised Dr. Kiessling, “Those degrees, along with a subsequent doctorate in Biochemistry/ Biophysics from Oregon State, became the educational foundation of her extraordinary career…”

UVA Alumni Award

In March, Dr. Kiessling was awarded the first ever Alumni Achievement Award by the University of Virginia School of Nursing. An enthusiastic crowd attended her talk, “Retroviruses, Reproduction, and Regenerative Medicine: The Influence of Federal Funding.” Watch the UVU Alumni Award video.

Victoria Staebler Joins The Foundation Board

The Foundation welcomes Victoria Staebler, Senior Financial Advisor at Merrill Lynch, to the Bedford Foundation Board of Trustees. Vicki holds degrees from Middlebury college and the University of Vermont, serves on the board of directors of The Boston Club, and has honorary board positions at PCI Media Impact, Inc. and Planned Parenthood of Northern New England.

New Lab Staff At The Foundation

We welcome two new staff members: Jacob Noble and Jack Vernamonti. Jake has a BS in physics and math from Northeastern University and is heading up the time-lapse, circadian rhythm, video projects. Jack has a BS in Biochemistry from Colby College and is Coordinator for the Special Program of Assisted Reproduction (SPAR), proudly announcing the birth of 157 babies free of HIV infection.

A Letter From The Director About Research At The Foundation

Our new century has brought world-wide turmoil to social structures, weather patterns, and the earth’s crust itself. Amidst financial collapses, government renewals, tsunamis, hurricanes and earthquakes, people all over the world are redefining “normal.”

So too with biomedical research. Gone is the paradigm of dependence on the federal government for basic research funding: the National Institutes of Health (NIH) can only fund about 10% of submitted grant applications from outside institutions, and that will not change for the foreseeable future. In addition, since funding “sure bets” accounts for most of the federal research budget, speculative research will not be federally funded. And speculative research is where the big breakthroughs lie. As stated by the Pew Charitable Trusts: “If 90% of our funded projects succeed, we are not taking enough risks.”

As the world’s people and institutions struggle with how to do more with less, so must science. American scientists are fortunate in that since the inception of the U.S. tax code in 1917, exemptions have been granted for charitable giving, supporting the notion that citizens have the right to support public causes they believe in.

Despite the global turmoil, our new century has brought steady growth to the Bedford Research Foundation. Our goal is to dramatically improve the efficiency of deriving patient-specific stem cells from naturally pluripotent sources: unfertilized eggs and testis. The added value in doing this is the information we are gaining about embryo development, because to regenerate tissues (heart, spinal cord, immune system, pancreas, etc) we need to study how those tissues form in the mouse. Combined, the work will not only benefit the new field of regenerative medicine, but will also provide new insights into normal human development, perhaps providing avenues to side-step degenerative diseases.

My frustration about how much more we could accomplish each day with more people, more money, is balanced by pride in our ability to do more with less, and by gratitude to the supporters who believe in our mission and our goals, and to the exceptional committee members who meet to support our needs for research oversight. Our administrative costs are low, our ratio of new information/research dollar spent is high, our goals are lofty

With gratitude for your support,

Ann A Kiessling, PhD
Director, Bedford Research Foundation

Who is Bedford Research Foundation?

Philanthropy Is The Key To Continued Progress

The average cost of each experiment is $90,000. Because much of our overhead is covered by fee-for-service laboratory tests, 92% of every dollar donated goes directly toward these experiments. This innovative funding model allows Bedford Research scientists greater flexibility to move quickly in promising new research directions.

Continued progress requires meeting our annual funding goal of $450,000 in 2019.

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