Lipofuscin Degradation by Bacterial Hydrolases

German Institute of Human Nutrition

Principal Investigator: Tilman Grune
Research Team: Annett Braune, Annika Höhn, Tim Baldesperger

Prof. Grune is the Scientific Director of the German Institute of Human Nutrition and has been working on protein degradation of damaged proteins and aging.

Lipofuscin (LF) is a strongly oxidized material composed of covalently cross-linked proteins, lipids, and carbohydrates. Cellular LF increases with age and negatively correlates with the remaining life span of cells. Lipofuscin accumulation is especially pronounced in postmitotic cells (including cardiomyocytes and neurons) as these cells are unable to “dilute” their lipofuscin via cell division. LF by itself impairs cardiomyocyte function by declining its contractility. Importantly, no known mammalian enzyme degrades lipofuscin, therefore LF accumulates within the cell, mostly within the lysosomes.

Microorganisms, particularly bacteria, possess a wide array of enzymes that allow the degradation of any conceivable molecule formed in nature. The project, therefore, aims at identifying bacterial enzymes able to degrade LF. The project includes the following tasks:

  • isolation of human LF and identification of its components,
  • identification of microbial hydrolases able to degrade LF, and
  • testing the effect of identified hydrolases and their products in living cardiomyocytes.

Research Highlights:

Prof. Grune has previously studied the role of lipofuscin in proteasomal inhibition in human cell culture models using artificial lipofuscin. Later, he worked with isolated lipofuscin from human retinal epithelial cells and described the effects of this material on microglial cells. After securing a reliable source of human hearts, the Grune team began isolating real tissue lipofuscin. They are presently working to analyze composition and quantify degradation of LF.  In recent years, the team has also worked with “artificial” lipofuscin and shown in a preliminary experiment that degradation by bacterial enzymes is possible. Upgrades to primary human material will allow optimization of the process of identifying bacterial enzymes with the ability to degrade the material.

Catalyzing Degradation of Tau Aggregates

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  • Team Members
  • Publications
  • Photos
  • Funding
  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding

Tau is the major microtubule-associated protein (MAP) in mature neurons in the central nervous system. The MAPT (microtubule-associated protein tau) gene encodes for six splice variants that are highly soluble; their main function is interacting and stabilizing microtubules, along with other MAPs. The ability of tau to stabilize the microtubule is aided by its phosphorylation.

Hyperphosphorylation of tau depresses its biological activity and can lead to destabilization of microtubules. Also, hyperphosphorylation of tau proteins can cause it to aggregate into oligomers, which in turn assemble into helical and straight insoluble filaments and ultimately mature into neurofibrillary tangles (NFTs).

In Alzheimer’s disease brain, tau is three to four-fold more hyperphosphorylated than in the normal adult brain, leading to a pathological buildup of NFTs. The accumulation of NFTs comprising hyperphosphorylated tau is also observed in normal aging (PMID: 24548606).

Various other neurodegenerative diseases, collectively called tauopathies – including Pick’s disease, corticobasal degeneration, progressive supranuclear palsy, frontotemporal lobar dementia with Parkinsonism linked to chromosome 17 (FTDP-17), and dementia pugilistica – are also caused by tau aggregation.

In consultation with SRF-supported biotech company Covalent Bioscience, SENS Research Foundation has initiated a project to develop a novel way to remove abnormally aggregated tau as a therapeutic intervention with potential relevance to mitigating normal age-dependent cognitive decline, as well as for tauopathies like Alzheimer’s disease and related dementias.

Covalent Bioscience have previously demonstrated the therapeutic potential of catabodies in a recent publication targeting Transthyretin (TTR) that forms misfolded b-sheet aggregates responsible for age-associated amyloidosis. In this paper they have described catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR) (PMID: 24648510).

Team Members

We’re Hiring!

Please visit the Work With Us page to learn about available positions.

Principal Investigator

Dr. Amit Sharma

Dr. Amit Sharma

Dr. Amit Sharma was awarded a Master’s degree in Biomedical Sciences from Delhi University, India.  He received his PhD in 2009 in Biotechnology from University of Pune for his work demonstrating microRNA regulation of cytokines involved in allergic inflammation in mice model. Dr. Sharma’s postdoctoral research at the Buck Institute, Novato California involved investigating novel molecular regulatory pathways involved in genotoxic stress and cellular senescence in invertebrate and mammalian models.

Dr. Sharma has recently joined SENS Research Foundation as Group Lead in the Senescence Immunology Research Group. His research focus involves studying how aging and senescence affects the immune system and his research group will also investigate strategies to harness the immune system in mitigating deleterious effects of senescent cells with translational focus.

Publications

Previous Publications by Dr. Sharma

Sharma A, Kumar M, Aich J, Hariharan M, Brahmachari S.K, Agrawal A and Ghosh B. Post-Transcriptional Regulation of Interleukin-10 Expression by hsa-miR-106a. Proc Natl Acad Sci U S A. 2009; 106: 5761-6. PMC 2659714

Sharma A, Kumar M, Ahmad T, Mabalirajan U, Aich J, Agrawal A and Ghosh B. Antagonism of mmu- mir-106a attenuates asthma features in allergic murine model. JAP, 2012.

Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, Ghosh B. Let-7 microRNA- mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol. 2011. PMID 21616524 

Kumar S, Sharma A and Madan B, Singhal V and Ghosh B. Isoliquiritigenin inhibits IkappaB kinase activity 
and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human 
endothelial cells. Biochem Pharmacol. 2007; 73:1602-12. 


Tanveer A, Mabalirajan U, Sharma A, Ghosh B, Agrawal A. Simvastatin Improves Epithelial Dysfunction 
and Airway Hyperresponsiveness: From ADMA to Asthma. Am J Respir Cell Mol Biol. 2011 Apr;44 (4):531- 
9. PMID 2055877

Ghosh B, Kumar S, Balwani S, Sharma A. Cell adhesion molecules: therapeutic targets for developing 
novel anti-inflammatory drugs. Advanced Biotech. 2005; 4:13-20. 


Sharma S, Sharma A, Kumar S, Sharma S.K. and Ghosh B. Association of TNF haplotypes with Asthma, 
Serum IgE levels and correlation with serum TNF-α levels. Am J Respir Cell Mol Biol. 2006; 35: 488-95.

Sharma A, Joseph Wu. MicroRNA Expression Profiling of Human Induced Pluripotent and Embryonic Stem Cells. Methods in molecular biology, a part in Springer Science. PMC 3638037

Sharma A, Diecke S, Zhang WY, Lan F, He C, Mordwinkin NM, Chua KF, Wu JC. The role of SIRT6 protein in aging and reprogramming of human induced pluripotent stem cells. J Biol Chem. 2013. PMID 23653361.

Lang S, Bose N, Wilson K, Brackman D, Hilsabeck T, Watson M, Beck J, Sharma A, Chen L, Killlilea D, Ho S, Kahn A, Giacomini K, Stoller M, Chi T, Kapahi P. A conserved role of the insulin-like signaling pathway in uric acid pathologies revealed in Drosophila melanogaster. bioRxiv 387779

Akagi K, Wilson K, Katewa SD, Ortega M, Simmons J, Kapuria S, Sharma A, Jasper H, Kapahi P. Dietary restriction improves intestinal cellular fitness to enhance gut barrier function and lifespan in D. melanogaster. PloS Genet. 2018 Nov 1; 14(11):e1007777. PMC6233930.

Sharma A, Akagi K, Pattavina B, Wilson KA, Nelson C, Watson M, Maksoud E, Ortega M, Brem R, Kapahi P. Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal homeostasis and survival in Drosophila. Sci Reports. 2020 Nov 5;10(1):19080.

Full list of published work as found in My Bibliography:

https://www.ncbi.nlm.nih.gov/sites/myncbi/amit.sharma.2/bibliography/55316754/public/?sort=date&direction=ascending

Photos

Resources

Funding

To support our work please consider making a donation to SENS Research Foundation!

Thanks to our existing funders:

Engineering New Mitochondrial Genes to Restore Mitochondrial Function (MitoSENS)

  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding
  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding

Mitochondria perform and support several vital functions in a cell, and the alternate genome, mtDNA, plays a critical role in organelle maintenance. There is increasing evidence that mitochondrial function declines with age, and that dysfunctional mitochondria adversely contribute to several metabolic and neuromuscular diseases. Our goal is to address age-acquired and inborn errors of mutation in the mtDNA using a gene therapy approach. We are exploring:

  1. allotopic expression (expressing mtDNA genes from the nucleus), and
  2. whole-organelle replacement

as strategies to revitalize mitochondrial function. Our multidisciplinary approach employs cell culture and mouse models to achieve our objectives.

Allotopic Expression of Proteins Encoded in the Mitochondrial DNA

Mitochondria are the ‘power plants’ in every mammalian cell responsible for the efficient conversion of nutrients to energy. Impaired mitochondrial function and mutations in mtDNA contribute to several age-related illnesses, including Alzheimer’s Disease, Parkinson’s disease, and sarcopenia. Point mutations in any of the 13 protein-coding regions, as well as micro- and macro- deletions in the mtDNA, lead to several monogenic and organelle-specific diseases (MELAS, MEERF, LHON, Leigh’s disease to name a few). However, alterations in the OriH / OriL regions in the mtDNA can lead to global impairment in the transcription and translation of the mitochondrial genome. The mitochondrial proteome, however, consists of ~1400 proteins of which all except for the 13 polypeptides translated on the mitochondrial genome originate from the host’ nucleus. Over the course of evolution, mitochondria have developed sophisticated mechanisms to import these nuclear mitochondrial proteins. These mechanisms employ intricate translocases and signals, which are directed to different regions within the organelle.

The goal of this project is to determine how we might achieve optimal parameters for coding and non-coding regions to efficiently express and target the 13 mtDNA genes to the respiratory chain from the nucleus. Toward this end, we employ molecular biology, biochemistry and computational strategies, and refine and build on our existing knowledge of import conditions for the numerous nuclear mitochondrial proteins already delineated. We use patient-derived cybrids and animal models in assessing the functional utility of our constructs. Ultimately, we aim to express the mtDNA genes individually or in combination to overcome age-related changes to the mtDNA and improve overall organelle fitness. Please see here for recent progress on this project.

Reversing Age-Induced Mitochondrial Damage through Organelle Transplantation

Intercellular mitochondria exchange occurs naturally in the human body between cell types, typically between healthy and damaged cells. Three different transfer mechanisms have been observed:

  1. stem cells release naked mitochondria that are taken up by other cells,
  2. mitochondria are released extracellularly, enclosed in vesicles that are in turn taken up by recipient cells (possibly via endocytosis), or
  3. mitochondria migrate from one cell to another through specialized structures in vivo, such as nanotubes.

The goal of this project is to evaluate the potential of mitochondrial transfer to counteract age-related loss of tissue function. We aim to develop strategies to purify viable mitochondria and deliver them to target regions in the body.

Team Members

We’re Hiring!

Please visit the Work With Us page to learn about available positions.

Principal Investigator

amutha-boominathan

Amutha Boominathan, PhD

Research Staff

BhavnaDixit-1a-o

Bhavna Dixit, MS (Research Associate II)

begelman

David Begelman, BS (Research Associate I)

Carly Truong_headshot

Carly Truong, BS (Research Technician)

Postbaccalaureate Fellows

Summer Scholars

Placeholder-Person-1

Jay-Miguel Fonticella (Class of 2022, Tufts University, BS)

Emily Wallace_headshot

Emily Wallace (Class of 2024, U Mich. BSE)

Lab Alumni

Research Staff

  • Jayanthi Vengalam (2012-2015) – now at Protagonist Therapeutics
  • Shon Vanhoozer (2014-2017)
  • Kathleen Powers (2015-2017) – now at Bristol Myers Squibb
  • Caitlin Lewis (2017-2021) – now at SENS Research Foundation CSO Team

Summer Scholars and Postbaccalaureate Fellows

Publications

Photos

Resources

Funding

To support our work please consider making a donation to SENS Research Foundation!

Thanks to our existing funders:

The Foster Foundation

Enhancing Innate Immune Surveillance of Senescent Cells

  • Research Info
  • Team Members
  • Publications
  • Resources
  • Photos
  • Funding
  • Research Info
  • Team Members
  • Publications
  • Resources
  • Photos
  • Funding

When normal cells lose their ability to replicate, they become senescent cells. Over time, senescent cells accumulate in aging tissues, spewing off a cocktail of inflammatory and growth factors, as well as enzymes that break down surrounding tissue and cause inflammation. This phenomenon is known as the “senescence-associated secretory phenotype” (SASP). Senescent cells – and the downstream impact of the SASP – are now implicated in a remarkable litany of the diseases of aging.

On a more encouraging note, multiple studies have now documented that “senolytic” drugs and gene therapies that destroy senescent cells exert sweeping rejuvenating effects in aging, both in laboratory animals and animal models of multiple diseases of aging. In theory, however, senolytic therapies shouldn’t be necessary. The body’s immune system is on continuous patrol against senescent cells: our natural killer (NK) cells recognize senescent cells as abnormal, bind to them, and release substances that trigger the senescent cells to self-destruct.

An SRF-donor-funded collaboration between Dr. Judith Campisi’s lab at the Buck Institute and the SRF Research Center seeks to discover why senescent cells accumulate with age, and what might we do to enhance immune surveillance and elimination of these cellular saboteurs?

Research Highlights:

The Campisi lab has recently published three papers describing the underlying mechanism of immune evasion by resistant senescent cells (Pereira et al., 2019, Munoz et al., 2019, and Kale et al., 2020). Dr. Campisi has found that a significant proportion of senescent cells manage to evade destruction, even by fresh NK cells. These ‘resistant’ cells escape immunosurveillance and accumulate in aging tissues. Senescent cells moreover shed decoy ligands binding to NK cell receptors; another aim of this work is to screen for more such ligands shed by senescent cells.

The Buck-SRF-RC collaboration is now seeking to drill further into the mechanism of senescent cell accumulation, and test interventions. At the SRF-RC, we are currently perfecting the method of co-culturing NK and senescent cells and controlling the killing process;  next, we will begin testing therapeutic interventions.

The SRF-RC scientists are also working for the first time with NK cells derived directly from aged human donors (rather than long-cultured lines of NK cells, or NK cells artificially “aged” by exposure to oxidative stress or extensive replication in culture, as has been done in the past). Using these cells will allow them to observe any direct effects of aging on NK cell senolytic activity.

Goals:

The primary goal of the laboratory is to find ways to avoid the accumulation with a focus on the immune system:

  • Reversing diminished immune surveillance
  • Use of NK cells to remove senescent cells

Goal 1: Natural killer cells are primary drivers of immune surveillance of senescent cells. This project involves isolation and characterization of age-dependent changes in the phenotypes of Natural Killer cells. This is to investigate if the age of subjects effects the ability of NK cells to eliminate senescent cells in vitro and in vivo.

Goal 2: We have identified several unique antigens expressed on the surface of senescent cells. The goal of this project is the targeted elimination of senescent cells by CAR-NK therapy. We are characterizing the surface an antigen on senescent cells and investigate if targeting this antigen can enhance NK cell-mediated clearance of senescent cells from patient-derived primary endothelial cells and fetal lung fibroblasts. The ultimate goal of the project is to demonstrate that the CAR-NK cells that are capable of eliminating senescent cells in ex vivo and mouse models.

Goal 3: Senescent cells are known to secrete a unique mixture of proinflammatory cytokines, chemokines and matrix modifying proteins called the SASP (Senescence Associated Secretory Phenotype). We have identified several SASP factors that may block immune surveillance by NK cells. Proof of principle experiments are currently being performed to investigate if selective removal of specific SASP factors can enhance immune surveillance of senescent cells. The long-term goal of this project is to develop therapeutic interventions based on removal of these SASP proteins for aging and related diseases.

Team Members

We’re Hiring!

Please visit the Work With Us page to learn about available positions.

Principal Investigator

Dr. Amit Sharma

Dr. Amit Sharma

Dr. Amit Sharma was awarded a Master’s degree in Biomedical Sciences from Delhi University, India.  He received his PhD in 2009 in Biotechnology from University of Pune for his work demonstrating microRNA regulation of cytokines involved in allergic inflammation in mice model. Dr. Sharma’s postdoctoral research at the Buck Institute, Novato California involved investigating novel molecular regulatory pathways involved in genotoxic stress and cellular senescence in invertebrate and mammalian models.

Dr. Sharma has recently joined SENS Research Foundation as Group Lead in the Senescence Immunology Research Group. His research focus involves studying how aging and senescence affects the immune system and his research group will also investigate strategies to harness the immune system in mitigating deleterious effects of senescent cells with translational focus.

Postdoctoral Fellow

Research Associate

Kristie_web

Kristie Kim
Identification and characterization of the surfaceome of senescent cells and development of CAR-NK cells to enhance immune surveillance

Postbaccalaureate Fellow

Gina Zhu (Postbaccalaureate Fellow, 2020-2021)
Identifying Novel Mechanisms to Enhance Natural Killer Cell Mediated Surveillance and Clearance of Senescent Cells

Summer Scholar

Chloe Amber Lindberg (Summer Scholar, 2021)
Investigating the effect of senescence-associated secretory phenotype (SASP) factors on NK cell function

Lab Alumni

Elena Fulton (Postbaccalaureate Fellow, 2019-2020)
Characterization of age dependent changes in peripheral NK cell phenotypes in humans

Mikayla Stabile (Summer Scholar, 2020)
Characterization of age dependent changes in peripheral NK cell phenotypes in humans

Publications

  • Kale A, Sharma A, Stolzing A, Desprez PY, Campisi J. Role of immune cells in the removal of deleterious senescent cells. Immun Ageing 2020 Jun 3;17:16. PubMed: 32518575.

Previous Publications by Dr. Sharma

Sharma A, Kumar M, Aich J, Hariharan M, Brahmachari S.K, Agrawal A and Ghosh B. Post-Transcriptional Regulation of Interleukin-10 Expression by hsa-miR-106a. Proc Natl Acad Sci U S A. 2009; 106: 5761-6. PMC 2659714

Sharma A, Kumar M, Ahmad T, Mabalirajan U, Aich J, Agrawal A and Ghosh B. Antagonism of mmu- mir-106a attenuates asthma features in allergic murine model. JAP, 2012.

Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, Ghosh B. Let-7 microRNA- mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol. 2011. PMID 21616524 

Kumar S, Sharma A and Madan B, Singhal V and Ghosh B. Isoliquiritigenin inhibits IkappaB kinase activity 
and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human 
endothelial cells. Biochem Pharmacol. 2007; 73:1602-12. 


Tanveer A, Mabalirajan U, Sharma A, Ghosh B, Agrawal A. Simvastatin Improves Epithelial Dysfunction 
and Airway Hyperresponsiveness: From ADMA to Asthma. Am J Respir Cell Mol Biol. 2011 Apr;44 (4):531- 
9. PMID 2055877

Ghosh B, Kumar S, Balwani S, Sharma A. Cell adhesion molecules: therapeutic targets for developing 
novel anti-inflammatory drugs. Advanced Biotech. 2005; 4:13-20. 


Sharma S, Sharma A, Kumar S, Sharma S.K. and Ghosh B. Association of TNF haplotypes with Asthma, 
Serum IgE levels and correlation with serum TNF-α levels. Am J Respir Cell Mol Biol. 2006; 35: 488-95.

Sharma A, Joseph Wu. MicroRNA Expression Profiling of Human Induced Pluripotent and Embryonic Stem Cells. Methods in molecular biology, a part in Springer Science. PMC 3638037

Sharma A, Diecke S, Zhang WY, Lan F, He C, Mordwinkin NM, Chua KF, Wu JC. The role of SIRT6 protein in aging and reprogramming of human induced pluripotent stem cells. J Biol Chem. 2013. PMID 23653361.

Lang S, Bose N, Wilson K, Brackman D, Hilsabeck T, Watson M, Beck J, Sharma A, Chen L, Killlilea D, Ho S, Kahn A, Giacomini K, Stoller M, Chi T, Kapahi P. A conserved role of the insulin-like signaling pathway in uric acid pathologies revealed in Drosophila melanogaster. bioRxiv 387779

Akagi K, Wilson K, Katewa SD, Ortega M, Simmons J, Kapuria S, Sharma A, Jasper H, Kapahi P. Dietary restriction improves intestinal cellular fitness to enhance gut barrier function and lifespan in D. melanogaster. PloS Genet. 2018 Nov 1; 14(11):e1007777. PMC6233930.

Sharma A, Akagi K, Pattavina B, Wilson KA, Nelson C, Watson M, Maksoud E, Ortega M, Brem R, Kapahi P. Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal homeostasis and survival in Drosophila. Sci Reports. 2020 Nov 5;10(1):19080.

Full list of published work as found in My Bibliography:

https://www.ncbi.nlm.nih.gov/sites/myncbi/amit.sharma.2/bibliography/55316754/public/?sort=date&direction=ascending

Photos

Funding

To support our work please consider making a donation to SENS Research Foundation!

Thanks to our existing funders:

Job Opportunity: Research Associate / Scientist – Boominathan Lab (MitoSENS)

Job Type: Full-time
Number of Positions: 2
Title: Research Associate/Scientist – Boominathan Lab
Salary: Pay is salaried, commensurate with experience and local rates; typically from $55,000/year.

Qualifications:

  • Bachelor’s/Masters/PhD
  • Laboratory experience: 2 years (Preferred)

The Boominathan lab at SENS Research Foundation (www.sens.org) is hiring highly motivated Research Scientists / Associates for a project geared toward translational therapies for mitochondrial dysfunctions. SENS Research Foundation is located in the heart of Silicon Valley (Mountain View, CA) and is close to several premier research organizations and major biotech hubs. Ours is an exciting, cutting-edge non-profit organization dedicated to transforming the way the world treats aging. More detailed information can be found at http://sens.org/research/intramural/allotopic-expression.

The successful candidate will use in vitro, in vivo and stem cell models to address diseases due to mtDNA mutations. This research position is within a small but dynamic group that strives to develop a deep understanding and curative therapies using a gene therapy approach to treat mitochondrial myopathies. Qualified candidates will have a BS/MS in the biological sciences and at least 2 years of relevant work experience. Recent PhDs with an exposure to mitochondria biology will be considered for a Research Scientist position. Duties will include performing wet lab experiments, recording, and analyzing data, and presenting the results in formal meetings every 2-3 months.

The ideal applicant will have experience in tissue culture, microscopy, flow cytometry and molecular biology with an exposure to protein analysis and biochemical assays. Hands on experience working with rodents is highly desirable. Experience working with mitochondria or interest in protein modelling are a big plus, but not required.

Other qualities:

  • Problem-solving
  • Team player
  • Creativity and the ability to think beyond an experiment to envision the path to success
  • Capacity to adapt as priorities and requirements change
  • Ability to plan and document your work diligently
  • Excellent written and verbal communication skills in English
  • Positive spirit, a real drive for science

We offer an excellent benefits package including paid vacation and sick leave, fully covered health and dental insurance (inclusive of dependents), an FSA program, and a company-matched 401(k) plan, all of which is offered after a 90-day introductory period. SENS Research Foundation is an equal opportunity employer. We may sponsor a visa for international applicants.

The positions are available now and will be filled as soon as qualified candidates are found. Salary is commensurate with job experience.

TO APPLY:

Interested candidates should apply by emailing a cover letter stating their scientific interests and current CV to [email protected].

COVID-19 considerations:

All employees are to follow COVID restrictions, which will lighten as our workplace is vaccinated. All employees are expected to wear PPE. Vaccinating is strongly encouraged.

Job Opportunity: Postdoctoral Research Fellow – Catabody Project

Job Type: Full-time
Title: Postdoctoral Research Fellow – Catabody Project
Salary: Pay is salaried, commensurate with experience and local rates; typically around $60,000/year.

Qualifications:

  • Doctorate (Preferred)
  • Molecular biology: 2 years (Preferred)
  • Wet chemistry: 2 years (Preferred)

SENS Research Foundation (SRF) is hiring a postdoctoral research fellow for our Research Center (RC) located in Mountain View, CA. SRF is an exciting, cutting-edge non-profit dedicated to transforming the way the world researches and treats aging.

More detailed information can be found here.

We seek a postdoctoral fellow to join our small but dynamic immunology team led by Dr. Amit Sharma. The project geared towards developing a novel way to remove abnormal tau aggregation. The project is potentially relevant for developing therapeutic mitigation of normal age-dependent cognitive decline, as well as for tauopathies like Alzheimer’s Disease and Related Disorders. This project involves utilizing enzymatic antibodies to target toxic tau aggregates. As part of the project we will explore ways of delivering antibodies into cells. We will use human iPS derived neuronal cells as a model system to test the catalytic antibodies and confirm tau degradation. The project involves extensive use of cell culture and mice models and involves working with human blood samples, primary human cells, and mice tissue. Duties will include performing wet-lab experiments, recording and analyzing data, and presenting the results in meetings every 2-3 months.

Experience:

  • Ph.D. in chemical/biological sciences and substantial bench experience or several years of industry experience
  • immunology
  • antibody design/production/screening
  • general molecular biology techniques (such as quantitative real-time PCR, Western blot, immunofluorescence, ELISA.)
  • iPSC culturing and neuronal differentiation

Other qualities:

  • Problem-solving
  • Team player
  • Creativity and the ability to think beyond an experiment to envision the path to success
  • Capacity to adapt as priorities and requirements change
  • Ability to plan and document your work diligently
  • Excellent written and verbal communication skills in English
  • Positive spirit, a real drive for science

We offer an excellent benefits package including paid vacation and sick leave, fully covered health and dental insurance (inclusive of dependents), an FSA program, and a company-matched 401(k) plan, all of which is offered after a 90-day introductory period. SENS Research Foundation is an equal opportunity employer. The job offer comes with two years contract with the possibility of an extension. We may sponsor a visa for international applicants.

The position is available now and will be filled as soon as the qualified candidate is found. Salary is commensurate with the job title.

TO APPLY:

Interested candidates should apply by emailing a cover letter and current CV to [email protected].

COVID-19 considerations:

All employees are to follow COVID restrictions, which will lighten as our workplace is vaccinated. All employees are expected to wear PPE. Vaccinating is strongly encouraged.

Job Opportunity: Research Associate – Catabody Project

Job Type: Full-time
Title: Research Associate
Salary: Pay is salaried, commensurate with experience and local rates; typically around $55,000/year.

Qualifications:

  • Master’s (Preferred)
  • Laboratory experience: 1 year (Preferred)
  • Wet chemistry: 1 year (Preferred)

SENS Research Foundation (SRF) is hiring a Research Associate for our Research Center (RC) located in Mountain View, CA. SRF is an exciting, cutting-edge non-profit dedicated to transforming the way the world researches and treats age-related diseases. More detailed information can be found at our website: www.sens.org

We seek a Research Associate to join our small but dynamic immunology team led by Dr. Amit Sharma. The project geared towards developing a novel way to remove abnormal tau aggregation. The project is potentially relevant for developing therapeutic mitigation of normal age-dependent cognitive decline, as well as for tauopathies like Alzheimer’s Disease and Related Disorders. This project involves utilizing enzymatic antibodies to target toxic tau aggregates. As part of the project we will explore ways of delivering antibodies into cells. We will use human iPS derived neuronal cells as a model system to test the catalytic antibodies and confirm tau degradation. The project involves extensive use of cell culture and mice models and involves working with human blood samples, primary human cells, and mice tissue. Duties will include performing wet-lab experiments, recording and analyzing data, and presenting the results in meetings every 2-3 months.

The ideal candidate for this full-time position has a Ph.D. in chemical/biological sciences and substantial (or the master’s degree with at least 1-2 years) bench experience, industry experience position is preferred. The candidate must be adaptable, a team player, self-motivated, and interested in problem-solving. Duties will include performing wet-lab experiments, recording and analyzing data, and presenting the results in meetings every 2-3 months.

The ideal candidate must have experience with molecular biology techniques, such as quantitative real-time PCR, Western blot, immunofluorescence, ELISA, microplate readers, and flow cytometry analysis, as well as prior experience performing data analysis and presenting data. Preference will be given to candidates with experience in primary cell culture and PBMC isolation from human blood.

We offer an excellent benefits package including paid vacation and sick leave, fully covered health and dental insurance (inclusive of dependents), an FSA program, and a company-matched 401(k) plan, all of which is offered after a 90-day introductory period. SENS Research Foundation is an equal opportunity employer. The job offer comes with two years contract with the possibility of an extension. We may sponsor a visa for international applicants.

The position is available now and will be filled as soon as the qualified candidate is found. Salary is commensurate with the job title.

TO APPLY:

Interested candidates should apply by emailing a cover letter and current CV to [email protected].

COVID-19 considerations:

All employees are to follow COVID restrictions, which will lighten as our workplace is vaccinated. All employees are expected to wear PPE. Vaccinating is strongly encouraged.

Job Opportunity: Postdoctoral Research Fellow – Senescence Immunology

Job Type: Full-time
Title: Postdoctoral Research Fellow – Senescence Immunology
Salary: Pay is salaried, commensurate with experience and local rates; typically around $60,000/year.

Qualifications:

  • Doctorate (Preferred)
  • Molecular biology: 2 years (Preferred)
  • Wet chemistry: 2 years (Preferred)

SENS Research Foundation (SRF) is hiring a postdoctoral research fellow for our Research Center (RC) located in Mountain View, CA. SRF is an exciting, cutting-edge non-profit dedicated to transforming the way the world researches and treats age-related diseases. More detailed information can be found at our website: www.sens.org

We seek a postdoctoral fellow to join our small but dynamic immunology team led by Dr. Amit Sharma for a project geared toward investigating the mechanisms involved in the age-dependent decline in immune surveillance of senescent cells with the aim of finding promising interventions.

There are three main projects currently for the postdoctoral fellow. One of the projects involves characterizing age-dependent phenotypes changes in the of Natural Killer cells and its implication on their ability to eliminate senescent cells in cell culture and mice model. We have identified several unique antigens expressed on the surface of senescent cells. The goal of the second project is to characterize the surface antigens on senescent cells and with the goal of developing CAR-NK cells with therapeutic application. The projects will require validating the CAR-NK cells in cell culture and the mice models of senescence. Senescent cells are known to secrete a unique mixture of proinflammatory cytokines, chemokines and matrix modifying proteins called SASP (Senescence Associated Secretory Phenotype). We have identified several SASP factors that may block immune surveillance by NK cells. The aim of the third project is to develop therapeutic interventions based on removal of these SASP proteins for enhancing immune surveillance of senescent cells in aging and senescence mice model. All these projects involve extensive use of cell culture and mice models and involves working with human blood samples, primary human cells, and mice tissue.

The ideal candidate for this full-time position has a Ph.D. in chemical/biological sciences and substantial bench experience. The candidate must be adaptable, a team player, self-motivated, and interested in problem-solving. The prospective postdoc will work closely with the Primary Investigator (PI) on a couple of projects with the potential of landing senior authorships in research publications resulting from the work. Duties will include performing wet-lab experiments, recording and analyzing data, and presenting the results in meetings every 2-3 months. The candidate also will be encouraged to present their findings in relevant national and international conferences and relevant scientific journals.

The ideal candidate must have experience with molecular biology techniques, such as quantitative real-time PCR, Western blot, immunofluorescence, ELISA, microplate readers, and flow cytometry analysis, as well as prior experience performing data analysis and presenting data. Preference will be given to candidates with experience in primary cell culture and PBMC isolation from human blood.

We offer an excellent benefits package including paid vacation and sick leave, fully covered health and dental insurance (inclusive of dependents), an FSA program, and a company-matched 401(k) plan, all of which is offered after a 90-day introductory period. SENS Research Foundation is an equal opportunity employer. The job offer comes with two years contract with the possibility of an extension. We may sponsor a visa for international applicants.

The position is available now and will be filled as soon as the qualified candidate is found. Salary is commensurate with the job title.

TO APPLY:

Interested candidates should apply by emailing a cover letter and current CV to [email protected].

COVID-19 considerations:

All employees are to follow COVID restrictions, which will lighten as our workplace is vaccinated. All employees are expected to wear PPE. Vaccinating is strongly encouraged.

Job Opportunity: Research Associate – Senescence Immunology

Job Type: Full-time
Title: Research Associate
Salary: Pay is salaried, commensurate with experience and local rates; typically around $55,000/year.

Qualifications:

  • Master’s (Preferred)
  • Laboratory experience: 1 year (Preferred)
  • Wet chemistry: 1 year (Preferred)

SENS Research Foundation (SRF) is hiring a Research Associate for our Research Center (RC) located in Mountain View, CA. SRF is an exciting, cutting-edge non-profit dedicated to transforming the way the world researches and treats age-related diseases. More detailed information can be found at our website: www.sens.org

We seek a Research Associate (RA) to join our small but dynamic immunology team led by Dr. Amit Sharma for a project geared toward investigating the mechanisms involved in the immune surveillance of senescent cells with the aim of finding promising interventions.

There are three main projects currently for the RA. One of the projects involves characterizing age-dependent phenotypes changes in the of Natural Killer cells and its implication on their ability to eliminate senescent cells in cell culture and mice model. We have identified several unique antigens expressed on the surface of senescent cells. The goal of the second project is to characterize the surface antigens on senescent cells and with the goal of developing CAR-NK cells with therapeutic application. The projects will require validating the CAR-NK cells in cell culture and the mice models of senescence. Senescent cells are known to secrete a unique mixture of proinflammatory cytokines, chemokines and matrix modifying proteins called SASP (Senescence Associated Secretory Phenotype). We have identified several SASP factors that may block immune surveillance by NK cells. The aim of the third project is to develop therapeutic interventions based on removal of these SASP proteins for enhancing immune surveillance of senescent cells in aging and senescence mice model. All these projects involves extensive use of cell culture and mice models and involves working with human blood samples, primary human cells, and mice tissue.

The ideal candidate for this full-time position has a Ph.D. in chemical/biological sciences and substantial (or the master’s degree with at least 1-2 years) bench experience, industry experience position is preferred. The candidate must be adaptable, a team player, self-motivated, and interested in problem-solving. Duties will include performing wet-lab experiments, recording and analyzing data, and presenting the results in meetings every 2-3 months.

The ideal candidate must have experience with molecular biology techniques, such as quantitative real-time PCR, Western blot, immunofluorescence, ELISA, microplate readers, and flow cytometry analysis, as well as prior experience performing data analysis and presenting data. Preference will be given to candidates with experience in primary cell culture and PBMC isolation from human blood.

We offer an excellent benefits package including paid vacation and sick leave, fully covered health and dental insurance (inclusive of dependents), an FSA program, and a company-matched 401(k) plan, all of which is offered after a 90-day introductory period. SENS Research Foundation is an equal opportunity employer. The job offer comes with two years contract with the possibility of an extension. We may sponsor a visa for international applicants.

The position is available now and will be filled as soon as the qualified candidate is found. Salary is commensurate with the job title.

TO APPLY:

Interested candidates should apply by emailing a cover letter and current CV to [email protected].

COVID-19 considerations:

All employees are to follow COVID restrictions, which will lighten as our workplace is vaccinated. All employees are expected to wear PPE. Vaccinating is strongly encouraged.

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