The SRF Summer Scholars Program offers undergraduate students the opportunity to conduct biomedical research to combat diseases of aging, such as cancer, Alzheimer’s, and Parkinson’s Disease. Under the guidance of a scientific mentor, each Summer Scholar is responsible for his or her own research project in such areas as genetic engineering and stem cell research. The Summer Scholars Program emphasizes development of both laboratory and communication skills to develop well-rounded future scientists, healthcare professionals, and policy makers. Students participating in the program will hone their writing skills via periodic reports, which are designed to emulate text scientists commonly must produce. At the end of the summer, students will have the opportunity to put all of their newly developed communication skills into practice at a student symposium.
SRF Education undergraduate programs primarily are designed to address two pressing needs in STEM education: the availability of novel, inquiry-based research opportunities and scientific communication skills. Whether a student plans to pursue postgraduate studies or apply for a research position at a pharmaceutical company, practical experience is key. However, research opportunities are limited at some colleges, and specific fields of research, such as tissue engineering, may be completely absent.
SRF Education sets itself apart from many other training programs with its focus on the development of scientific communication skills in addition to enhancing laboratory and critical thinking skills. Over the course of its educational programs, participants are guided through practical writing assignments that simulate documents scientists are often asked to produce, such as grant proposals. The communication training culminates in a formal presentation at a symposium where participants present the results of their work to their peers and mentors.
Review the following to confirm your eligibility to participate in the program:
If you have any questions regarding your eligibility for the program, you may contact SRF Director of Education Gregory Chin at [email protected].
Below is an alphabetical list of the Principal Investigators (PIs) and their 2021 Summer Scholar research projects. Additional projects may be added when applications for the program open.
Aß oligomers (AßO) are the toxic species thought by many to drive Alzheimer’s Disease. However, how AßO can drive neurodegeneration has been a long-standing debate that is as of yet unresolved. On the other hand, the study of senescence within the central nervous system (CNS) has recently began to emerge. Senescent cells can be deleterious by developing the senescence-associated secretory phenotype (SASP), which includes the release of inflammatory and oxidative factors. Senescence can also propagate autonomously by secondary senescence. Finally, outside of the brain, senescent cells can be cleared by natural killer cells, part of the innate immune system.
Our hypothesis is that AßO-induced senescence results in the SASP, causing inflammation, oxidative and proteotoxic stress conducive to cognitive impairment. Secondary senescence through neuronal projections can explain the spread of pathology. Finally, natural killer cell infiltration into the brain parenchyma amidst loss of blood brain barrier integrity can result in widespread senescent cell killing, potentially marking the onset of neuronal death in clinical AD. To test our hypotheses, we are assessing AßO-induced senescence in primary neuron cultures and natural killer cell co-cultures using histo-cytometry: which includes immunocytochemistry, spectral scanning plus linear unmixing confocal imaging, and image-data processing with IMARIS and FlowJo.
Mitochondria are the power plants of the cell and are also the only cellular organelle in mammals that possess their own DNA. In humans, mitochondrial DNA (mtDNA) codes for 13 important proteins, which all assemble into the oxidative phosphorylation relay. Mutations in mtDNA occur as a consequence of constant exposure to reactive oxygen species produced by the mitochondrial energy generation process as well as mistakes in mtDNA replication. These mutations accumulate over time due to inefficient repair mechanisms and compromised respiratory chain function. Inherited and acquired mutations in mtDNA result in impaired energy generation and are the cause for several pathologies, such as Leber’s hereditary optic neuropathy (LHON), Myoclonic Epilepsy with Ragged Red Fibers (MERRF), Kearns-Sayre syndrome, and Leigh syndrome.
At SENS Research Foundation, we are in the early stages of creating an exciting and innovative system to repair mitochondrial mutations. Using the allotopic approach, we have identified specific targeting elements/ sequences that can improve expression of these essential genes from the nuclear DNA and their transport to the correct location in mitochondria. The Summer Scholar selected will use a computational approach to design and test a library of constructs in model patient cell lines with specific mutations to mtDNA. The ability of re-engineered genes to rescue function will be evaluated through various techniques, such as protein gels, qPCR, and activity assays, with the potential of extending the studies to animal models.
Underdog Pharmaceuticals, a startup-level pharmaceutical company embedded in the SRF Research Center, is looking for a motivated Summer Scholar to join our team. Underdog is engineering drugs that can bind and reverse the pathological effects of certain oxidized forms of cholesterol implicated in atherosclerosis and several other diseases of aging. The laboratory techniques involved include isolation of peripheral blood mononuclear cells (PBMCs) and macrophages from human blood; flow cytometry to characterize macrophages in various states of differentiation, polarization, and disease; semi-automated (robotic liquid handler) biochemical binding and toxicity assays; ELISA; and other common molecular biology and biochemistry techniques. The choice of a specific project will depend on the skillset and preferences of the trainee. As an example, one project involves developing a new assay to accurately measure 7-keto cholesterol levels in tissue samples. Interested applicants do not need to know all the techniques required to run these assays but should be familiar with routine lab protocols and should not be uncomfortable working with human or animal blood and tissues.
Cancer is a complex disease caused by uncontrolled cell proliferation and it is the second leading cause of death globally. There is a dire need for rapid and cost effective screening platforms that also provide a physiologically relevant background that include host immunity and a complex tumor microenvironment. We will implement a high-throughput screening strategy using the multicellular organism C. elegans to identify anticancer compounds. Many of the pathways that when deregulated lead to tumor formation are conserved between humans and C. elegans. We found that a constitutively active mutant in the FGFR3 (Fibroblast Growth Factor Receptor 3) ortholog old-2 in C. elegans causes late-onset germ cell tumors and sterility similar to the ovarian tumors and late-onset testicular tumors observed due to a constitutively activating mutation in FGFR3 in humans. Utilizing a strain carrying a fluorescent reporter to track mitotic germ cells/tumors, animal viability and fertility in the old-2 constitutively active mutant we will perform a high-throughput screen to identify compounds that suppress tumor formation and rescue fertility while also controlling for drug toxicity.
The functions of the brain emerge from communication between neurons. The language of neuronal communication is mediated by chemicals that are released from one neuron and sensed by another. These chemical signals consistent of both “fast acting” neurotransmitters, as well as more than 200 neuromodulators that act on longer timescales. Neuropeptides are the largest and most diverse class of neuromodulators, and they control vital processes like energy homeostasis, as well as motivational and emotional states such as sleep, arousal, pain, stress, and mood. Yet, we still lack a clear understanding of how neuropeptides generate the diverse behavioral outputs of the brain. In particular, the molecular mechanisms by which neuropeptides are turned ‘off’ once they have been released from a neuron are not well understood. To address this challenge, we are systematically identifying neuropeptidases, the enzymes that turn off neuropeptide signaling, and mapping which neuropeptides they inactivate. We are seeking undergraduate student researchers to assist a postdoctoral scholar in the lab to characterize identified neuropeptidases and manipulate their expression within specific cell types to determine their role(s) in behavior and aging.
Desired Skills or Experience: Completed coursework in biology, biochemistry, chemistry, genetics, and neuroscience desired but not necessary. Familiarity and proficiency with the following techniques desirable: C. elegans maintenance, PCR, cloning, microscopy, mass spectrometry.
Rubedo Life Sciences is on a mission to extend healthspan by targeting the aging process with innovative drugs. This Venture Capital-backed early stage company is located in the heart of the Silicon Valley at state-of-the-art facilities, fully equipped for chemistry, molecular biology, cell biology and animal studies. We are looking for an enthusiast Summer Scholar to join our passionate team, which includes world-class leaders in aging, regenerative medicine, drug discovery, and computational sciences who joined Rubedo from top Pharma, Biotech or IT industries as well as Ivy League universities.
The Rubedo Summer Scholar will be exposed to a number of different fields across our departments, including: 1) bioinformatics and chemoinformatics; 2) cell engineering and molecular biology; and 3) in vivo preclinical studies. The Summer Scholar project will be part of our drug R&D programs aimed at new classes of drugs capable of killing senescent cells, pro-inflammatory and pro-fibrotic cell populations that accumulate in the body as a consequence of aging and pathological conditions. Over time, senescent cell accumulation drives chronic and degenerative diseases, such as neurodegenerative diseases, diabetes, lung diseases, cancer, sarcopenia, frailty, and, overall, accelerates aging itself. We and others have shown that targeted elimination of senescence in animal models results in improving or reverting age-related conditions with beneficial regenerative and rejuvenative effects. At Rubedo, we are translating these technologies into new medicines. You have now the chance to be part of these exciting endeavors.
Possible research project options include:
1) In Silico Target Discovery – Desired skills and experiences: bioinformatics, cheminformatics, machine learning, generative machine learning, generative chemistry, and data visualization
2) Preclinical Drug Development – Desired skills and experiences: assisting with rodent studies, histology and morphology, imaging analysis including applications with artificial intelligence, cell culture, and flow cytometry.
Cell-based therapies are emerging as a promising strategy to tackle cancer. We have developed tumor cell surface receptor targeted T cells and adult stem cells expressing novel bi-functional pro-apoptotic and immunomodulatory proteins and oncolytic viruses. Using different primary and metastatic tumor models that mimic clinical settings, we show that engineered stem cells expressing novel bi-functional proteins or loaded with oncolytic viruses target both the primary and the invasive tumor deposits and have profound anti-tumor effects. Recently, we have reverse engineered cancer cells using CRISPR/Cas9 technology and demonstrated self-tumor tropism and therapeutic potential of receptor self-targeted engineered cancer cells. These studies demonstrate the strength of employing engineered cells and real-time imaging of multiple events in preclinical-therapeutic tumor models and form the basis for developing novel cell based therapies for cancer.
Senescent cells are characterized by an irreversible arrest of the cell cycle. They secrete a unique milieu of pro-inflammatory cytokines, chemokines, and growth factors collectively referred to as the senescence-associated secretory phenotype (SASP). These cells have been implicated in a large number of age-related diseases, and recent efforts to develop therapeutic interventions are centered around either selectively eliminating senescent cells (senolytics) or reducing SASP secretion (senomorphics). While these approaches present two possible avenues for reducing senescent cells’ impact, they still lack specificity for their intended target.
We focus on developing therapeutic interventions to selectively eliminate senescent cells by utilizing innate immune cells like Natural Killer (NK) cells. These innate immune cells have evolved to selectively induce apoptosis in target cells that express ligands, such as senescent cells. However, recent studies have shown that some senescent cells employ mechanisms to escape NK-mediated clearance, while ‘aged’ NK cells become less efficient at eliminating target cells.
The laboratory focuses on enhancing the targeted elimination of senescent cells by NK cells. We are pursuing three main avenues of research:
These approaches will afford a better understanding of interactions between NK cells and senescent cells in the context of aging and help develop novel therapeutic interventions for enhanced elimination of senescent cells.
We believe the study of stem cell biology will provide insights into many areas: developmental biology, homeostasis in the normal adult, and recovery from injury. Indeed, past and current research has already produced data in these areas that would have been difficult or impossible via any other vehicle. We have engaged in a multidisciplinary approach, simultaneously exploring the basic biology of stem cells, their role throughout the lifetime of an individual, as well as their therapeutic potential. We have taken two disparate organ systems, the brain and the lung, and are discovering parallels in their development, response to infections and molecular functions. Taken together, these bodies of knowledge will glean the greatest benefit for scientists and, most importantly, for patients. All of our research to date has been performed in human stem cells and verified in animal models with the ultimate goal of bringing them to clinical trials as soon as possible.
Possible research project options include:
The Genotype-Tissue Expression (GTEx) project funded by NIH common fund has sequenced thousands of human tissue samples from around 1000 people and 56 different types of organs. One of the main aims is to understand the association of genetic variations to phenotypes. However, the massive data generated by GTEx not only can provide information to explain the variations but also can be used to study aging. The GTEx cohort contains all age groups, and the data provides molecular profiles from multi-omics. Most of the previous aging studies were done using animal models or with very limited clinic data. For a few large-scale studies, they are mainly based on genomic information in general. As part of the GTEx project, our lab has sequenced the proteome of multiple organs from many individuals. Compared to genomics, proteomics is closer to phenotype and can provide direct evidence. Integrating proteomics information with other omics can provide a more comprehensive molecular profile for the study of aging at organ level. However, integrating information from multi-omics is a daunting task. It requires knowledge from both domains and also needs sophisticated mathematical models. We believe results from this study will greatly advance the understanding of aging.
– The 2021 SRF Summer Scholars Program application period is now closed. –
The 2021 SRF Summer Scholars Program application period is now open.
Applications will be accepted until noon PST Friday, January 15, 2021 (12pm PST 1/15/21).
Please be sure to download the recommendation instructions and give your
recommender(s) ample time to submit your letter of recommendation by the deadline.
Offering recent graduates the opportunity to conduct biomedical research to combat diseases of aging under the guidance of a scientific mentor, with the goal of preparing participants for a career in regenerative medicine research.