The Forever Healthy Foundation Fellowship in Rejuvenation Biotechnology
Request for Proposals (RFP)
The Forever Healthy Foundation Fellowship in Rejuvenation Biotechnology
In cooperation with the Forever Healthy Foundation, SENS Research Foundation (SRF) is inviting candidates to submit research proposals for a Fellowship in Rejuvenation Biotechnology at our Research Center (RC) in Mountain View, California.
Applications are requested that promise progress in clearly describable milestones during the period of the Fellowship in any area of Rejuvenation Biotechnology – defined as the application of the principles of regenerative medicine for the prevention and reversal of age-related disease. Degenerative aging is a consequence of the progressive accumulation of damage to tissue cellular and molecular structures over time; specific diseases of aging emerge when the cumulative burden of such damage in a particular tissue exceeds the minimum required to sustain its core biological functions. SRF thus pursues the development of therapies to prevent and reverse age-related disease and disability through a “damage-repair” paradigm: developing interventions that maintain and restore the structural and functional integrity of tissues by directly removing, repairing, replacing, or rendering harmless the cellular and molecular damage of aging.
Successful candidates will be given support for a three-year project, to be carried out at the RC. Support includes salary for the Fellow, benefits, supplies, and space in our fully equipped research lab. Nearby universities available for collaboration include Stanford, UCSF, UC Berkeley, The Buck Institute for Research on Aging, and UC Santa Cruz.
Successful proposals will have significant translational potential, will clearly identify the form of cellular and molecular aging damage to be targeted, and will describe the strategy to be advanced towards its direct detection, removal, or repair. Successful applicants will also demonstrate the knowledge and skills necessary to independently complete their proposed research program.
In addition to a C.V. or NIH-style biosketch, please submit a Letter of Intent (LOI) of no more than 2 pages to outline your 3-year research project and your qualifications relevant to that project. Applicants must have a Ph.D. or other equivalent doctoral degree from any reputable domestic or international institution. Postdocs who are further removed from their PhD are welcome to apply, as are international applicants; visa support will be provided if hired.
The deadline for receipt of your LOI is May 15th 2018. A subset of applicants will be invited to submit a full research proposal for consideration. SRF is an equal opportunity employer. Interested candidates should submit their Letter of Intent as a single PDF document in the format “Your Name – RFP” to Foundation@sens.org.
Example research proposals: Proposals may be made in any area of rejuvenation biotechnology, but currently SRF is especially interested in the following areas:
Clearance of Persistent Intracellular Aggregates: Proteinaceous intracellular aggregates feature prominently in many diseases of aging, most notably those of neurodegenerative aging. Targeting various components of “lipofuscin” would be one strategy. However, some of the most important targets in this space (such as aberrant tau species and aggregated α-synuclein), accumulate in cytosolic inclusions.
SRF invites proposals for new strategies to clear such inclusions.
Identification and Targeting of Noncanonical Death-Resistant Cells: A variety of cell types with apparently deleterious effects accumulate in aging, of which the best understood are senescent cells. These cells are characterized by a state of irreversible growth arrest and by the secretion of factors that promote inflammation and other deleterious effects. Powerful evidence supporting this view has come from recent studies in which such cells are ablated in aging and disease-model mice by genetic or pharmacological means, leading to tissue rejuvenation and amelioration or prevention of models of age-related disease. These studies may not be capturing the full range of senescent cells or their possible contribution to degenerative aging, however, and may be missing important subtypes. Traditional senescent cell markers such as p16, p21, senescence-associated β-gal, TIFs, morphology, and b-laminin levels are likely not to be universal, and thus may limit ablation strategies that are dependent on one or more of these markers.
SRF invites proposals for novel strategies for discovering and targeting these non-canonical senescent cells, or other non-canonical cells accumulating aberrantly in aging tissues.
Regenerative Mobilization of Atherosclerotic Foam Cells: Atherosclerotic lesions are initiated by the accumulation of monocyte-derived macrophages in the arterial intima after their engulfment of oxidized LDL (oxLDL) through scavenger receptors. While the initial engulfment protects the vessel from injury, the toxicity of oxLDL to the macrophages themselves leads to pathological consequences as such cells release inflammatory and thrombotic cytokines, chemokines that recruit additional lymphocytes, and matrix metalloproteinases (MMPs) that thin the fibrous cap and promote its rupture. A pathological property of foam cells is their immobility: macrophages normally migrate away from sites of phagocytosis, but foam cells instead lay down focal adhesive contacts and accumulate in the vessel wall. Conversely, foam cell migration out of atherosclerotic plaque and into regional lymph nodes is the first and critical step in plaque regression induced by lipid-lowering via statins or severe energy restriction.
SRF invites proposals for research targeting the removal or mobilization of atherosclerotic lesional macrophages/foam cells.
Rejuvenation of the Aging Extracellular Matrix: The extracellular matrix (ECM) serves critical roles in tissue function, not only as a scaffold for parenchymal tissue and organ structure, but in interacting with and regulating cellular function, survival, proliferation, and growth. ECM is composed of multiple proteins and polysaccharides built on a scaffold of collagen, with the composition particular to each tissue. ECM structure is disrupted by aging processes, including alterations in protein synthesis and turnover, posttranslational modifications of structural proteins, and mechanical disruption. Age-related changes in ECM structure impair both the ECM’s structural functions and tissue and organ homeostasis.
SRF has for some years sponsored research on glycation and other crosslinking in aging tissues and means to cleave such crosslinks. We invite proposals for projects to rejuvenate this and other aspects of ECM aging.
Molecular Composition and Possible Origins of Cardiac Lipofuscin: The accumulation of uncharacterized fluorescent material in animal hearts with age was first reported in 1911, and human autopsy studies have since confirmed a substantial and generally linear accumulation in the aging human heart. However, little work has been done to characterize the composition of this material.
SRF invites proposals for a detailed investigation of the composition of cardiac lipofuscin, which could lead to therapeutic targets. Other proposals focused on age-related lipofuscin would also be of interest.