Biological Research Program Research Articles

Editorial introductions.

Editorial introductions.

A first insight into the genomic background of Ilex pubescens (Aquifoliaceae) by flow cytometry and genome survey sequencing

BackgroundIlex pubescens is an important traditional Chinese medicinal plant with many naturally occurring compounds and multiple pharmacological effects. However, the lack of reference genomic information has led to tardiness in molecular biology research and breeding programs of this plant.ResultsTo obtain knowledge on the genomic information of I. pubescens, a genome survey was performed for the first time by next generation sequencing (NGS) together with genome size estimation using flow cytometry. The whole genome survey of I. pubescens generated 46.472 Gb of sequence data with approximately 82.2 × coverage. K-mer analysis indicated that I. pubescens has a small genome of approximately 553 Mb with 1.93% heterozygosity rate and 39.1% repeat rate. Meanwhile, the genome size was estimated to be 722 Mb using flow cytometry, which was possibly more precise for assessment of genome size than k-mer analysis. A total of 45.842 Gb clean reads were assembled into 808,938 scaffolds with a relatively short N50 of 760 bp. The average guanine and cytosine (GC) content was 37.52%. In total, 197,429 microsatellite motifs were detected with a frequency of 2.8 kb, among which mononucleotide motifs were the most abundant (up to 62.47% of the total microsatellite motifs), followed by dinucleotide and trinucleotide motifs.ConclusionIn summary, the genome of I. pubescens is small but complex with a high level of heterozygosity. Even though not successfully applied for estimation of genome size due to its complex genome, the survey sequences will help to design whole genome sequencing strategies and provide genetic information support for resource protection, genetic diversity analysis, genetic improvement and artificial breeding of I. pubescens.

Counting with Cilia: The Role of Morphological Computation in Basal Cognition Research.

"Morphological computation" is an increasingly important concept in robotics, artificial intelligence, and philosophy of the mind. It is used to understand how the body contributes to cognition and control of behavior. Its understanding in terms of "offloading" computation from the brain to the body has been criticized as misleading, and it has been suggested that the use of the concept conflates three classes of distinct processes. In fact, these criticisms implicitly hang on accepting a semantic definition of what constitutes computation. Here, I argue that an alternative, mechanistic view on computation offers a significantly different understanding of what morphological computation is. These theoretical considerations are then used to analyze the existing research program in developmental biology, which understands morphogenesis, the process of development of shape in biological systems, as a computational process. This important line of research shows that cognition and intelligence can be found across all scales of life, as the proponents of the basal cognition research program propose. Hence, clarifying the connection between morphological computation and morphogenesis allows for strengthening the role of the former concept in this emerging research field.

Self-consistent numerical evaluation of concrete shielding activation for proton therapy systems

Due to the advancement of proton therapy for cancer treatment, there has been a worldwide increase in the construction of treatment facilities. Therapy centres are often coupled with clinical, biological or material-science research programs. Research activities require proton beams at energies spanning an extensive range with higher beam currents and longer irradiation times than clinical conditions. Additionally, next-generation proton therapy systems are evolving towards more compact designs. In addition to the increased centres’ workloads, reducing the system in size produces a more significant number of secondary particles per unit volume and time. Therefore, the activation level of materials constituting those future proton therapy centres is expected to be higher, increasing the ambient dose and the amount of radioactive waste collected at the end of a centre’s lifetime. These operating conditions pose new challenges for the shielding design and the reduction of the concrete activation. To tackle them, we propose a novel approach to seamlessly simulate all the processes relevant for the evaluation of the concrete shielding activation using, as an illustration, the Ion Beam Applications Proteus^circledR One system. A realistic model of the system is developed using Beam Delivery Simulation (BDSIM), a Geant4-based particle tracking code. It allows a single model to simulate primary and secondary particle tracking in the beamline, its surroundings, and all particle-matter interactions. The code system and library database FISPACT-II allows the computation of the shielding activation by solving the rate equations using ENDF-compliant group library data for nuclear reactions, particle-induced or spontaneous fission yields, and radioactive decay. As input, FISPACT-II is provided with the secondary particle fluences scored using the BDSIM Monte Carlo simulations. This approach is applied to the proton therapy research centre of Charleroi, Belgium. Results compare the evolution of the clearance level and the long-lived nuclide concentrations throughout the facility lifetime when using regular concrete or the newly developed Low Activation Concrete (LAC). A comparison with the initial shielding dimensioning has been performed for all the shielding walls to validate the methodology and highlight the clear benefits of integrating LAC inserts in the shielding design. The effectiveness of coupling BDSIM and FISPACT-II gives a glimpse of the possibility of a complete activation study following the actual workloads of the centre, allowing a better assessment of the shielding activation level at any time of the facility lifespan.

Editorial introductions.

Editorial introductions.

Massive economic costs of biological invasions despite widespread knowledge gaps: a dual setback for India

Biological invasions are one of the top drivers of the ongoing biodiversity crisis. An underestimated consequence of invasions is the enormity of their economic impacts. Knowledge gaps regarding economic costs produced by invasive alien species (IAS) are pervasive, particularly for emerging economies such as India—the fastest growing economy worldwide. To investigate, highlight and bridge this gap, we synthesised data on the economic costs of IAS in India. Specifically, we examine how IAS costs are distributed spatially, environmentally, sectorally, taxonomically, temporally, and across introduction pathways; and discuss how Indian IAS costs vary with socioeconomic indicators. We found that IAS have cost the Indian economy between at least US$ 127.3 billion to 182.6 billion (Indian Rupees ₹ 8.3 trillion to 11.9 trillion) over 1960–2020, and these costs have increased with time. Despite these massive recorded costs, most were not assigned to specific regions, environments, sectors, cost types and causal IAS, and these knowledge gaps are more pronounced in India than in the rest of the world. When costs were specifically assigned, maximum costs were incurred in West, South and North India, by invasive alien insects in semi-aquatic ecosystems; they were incurred mainly by the public and social welfare sector, and were associated with damages and losses rather than management expenses. Our findings indicate that the reported economic costs grossly underestimate the actual costs, especially considering the expected costs given India’s population size, gross domestic product and high numbers of IAS without reported costs. This cost analysis improves our knowledge of the negative economic impacts of biological invasions in India and the burden they can represent for its development. We hope this study motivates policymakers to address socio-ecological issues in India and launch a national biological invasion research programme, especially since economic growth will be accompanied by greater impacts of global change.

T–Cell Engineering for Chimeric Antigen Receptor T–Cell Therapy in Cancer

Through T-cell engineering, researchers at the California South University (CSU) Cancer Research Institute (CRI) have shown that tumor growth can be stopped in a variety of cancers and prevented from spreading to other tissues. Findings from this study are the result of decades of research by Professor Alireza Haidari, a member of the Cancer Biology Research Program at the California South University (CSU), who discovered a protein called AH that can inhibit the growth and spread of cancer cells in several different ways. They become in the tissues of the body. Keywords: Cancer; Cells; Tissues; Tumors; Prevention; Prognosis; Diagnosis; Imaging; Screening, Treatment; Management

T Cell Engineering as Therapy for Cancer and HIV

Through T-cell engineering, researchers at the California South University (CSU) Cancer Research Institute (CRI) have shown that tumor growth can be stopped in a variety of cancers and prevented from spreading to other tissues. Findings from this study are the result of decades of research by Professor Alireza Heidari, a member of the Cancer Biology Research Program at the California South University (CSU), who discovered a protein called AH that can inhibit the growth and spread of cancer cells in several different ways. They become in the tissues of the body. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

Einstein-Nathan Shock Center: translating the hallmarks of aging to extend human health span.

The overarching mission of the Einstein-Nathan Shock Center (E-NSC) is to make scientific discoveries in geroscience, leveraging on the expertise in our center in 6 out of the 7 pillars of aging, and to translate their effects towards drug discovery. The relevance of this basic biology of aging discoveries to humans will be confirmed through the unique gero-human resource at E-NSC. This is achieved through services provided by E-NSC, connectivity among its members, attracting worldwide investigators, and providing them with the opportunities to become future leaders. The two central components of the E-NSC are (a) cutting-edge research programs and (b) unique E-NSC research support cores. E-NSC scientists lead NIH-supported cutting-edge research programs that integrate key hallmarks of aging including proteostasis/autophagy, metabolism/inflammaging, genetic/epigenetics, stem cells/regeneration, and translational aging/longevity. Since the inception of the E-NSC, the well-integrated, collaborative, and innovative nature of the multiple supporting state-of-the-art E-NSC research cores form the bedrock of research success at the E-NSC. The three state-of-the-art E-NSC research cores, (i) Proteostasis of Aging Core (PAC), (ii) the Health Span Core (HSC), and (iii) the Human Multi-Omics Core (HMOC), have allowed impressive expansion of translational biological research programs. Expansion was facilitated through the wealth of data coming from genomics/proteomics and metabolomic analysis on human longevity studies, due to access to a variety of biological samples from elderly subjects in clinical trials with aging-targeting drugs, and new drug design services via the PAC to target the hallmarks of aging.

LiCoO2 Epitaxial Film Enabling Precise Analysis of Interfacial DegradationsSupported by the National Natural Science Fund for Innovative Research Groups (China) (Grant No. 51621003), the National Key Research and Development Program of China (Grant No. 2016Yu7FB0700700), the Beijing Municipal Fund for Scientific Innovation (Grant No. PXM2019 014204 500031) and the Beijing Municipal High Level Innovative Team Building Program (Grant No. IDHT20190503).

Interfacial structure evolution and degradation are critical to the electrochemical performance of LiCoO2 (LCO), the most widely studied and used cathode material in lithium ion batteries. To understand such processes requires precise and quantitative measurements. Herein, we use well-defined epitaxial LCO thin films to reveal the interfacial degradation mechanisms. Through our systematical investigations, we find that surface corrosion is significant after forming the surface phase transition layer, and the cathode electrolyte interphase (CEI) has a double layer structure, an inorganic inner layer containing CoO, LiF, LiOH/Li2O and Li x PF y O z , and an outmost layer containing Li2CO3 and organic carbonaceous components. Furthermore, surface cracks are found to be pronounced due to mechanical failures and chemical etching. This work demonstrates a model material to realize the precise measurements of LCO interfacial degradations, which deepens our understanding on the interfacial degradation mechanisms.

Standardization of electrolyte leakage data and a novel liquid nitrogen control improve measurements of cold hardiness in woody tissue

BackgroundA variety of basic and applied research programs in plant biology require the accurate and reliable determination of plant tissue cold hardiness. Over the past 50 years, the electrolyte leakage method has emerged as a popular and practical method for quantifying the amount of damage inflicted on plant tissue by exposure to freezing temperatures. Numerous approaches for carrying out this method and analyzing the resultant data have emerged. These include multiple systems for standardizing and modeling raw electrolyte leakage data and multiple protocols for boiling or autoclaving samples in order to maximize leakage as a positive control. We compare four different routines for standardization of leakage data and assess a novel control method—immersion in liquid nitrogen in lieu of traditional autoclaving—and apply them to woody twigs collected from 12 maple (Acer) species in early spring. We compare leakage data from these samples using each of four previously published forms of data analysis and autoclaving vs. liquid nitrogen controls and validate each of these approaches against visual estimates of freezing damage and differential thermal analysis.ResultsThrough presentation of our own data and re-analysis of previously published findings, we show that standardization of raw data against estimates of both minimum and maximum attainable freezing damage allows for reliable estimation of cold hardiness at the species level and across studies in diverse systems. Furthermore, use of our novel liquid nitrogen control produces data commensurate across studies and enhances the consistency and realism of the electrolyte leakage method, especially for very cold hardy samples.ConclusionFuture leakage studies that relativize data against minimum and maximum leakage and that employ our updated liquid nitrogen control will contribute generalizable, repeatable, and realistic data to the existing body of cold hardiness research in woody plants. Data from studies conducted using a liquid nitrogen (and not an autoclaving) control can still be compared to previously published data, especially when raw data are standardized using the best-performing approach among those we assessed. Electrolyte leakage of woody twigs emerges as a useful technique for quickly assessing the probability of tissue death in response to freezing in dormant plants. Differential thermal analysis may provide different and complementary information on cold hardiness.

The Ecology Underground coalition: building a collaborative future of belowground ecology and ecologists.

Rising to meet global, interconnected challenges, such as food security and ecosystem resilience to global change, requires insights from across the Earth. This is especially true for belowground terrestrial ecological processes. Soil ecologists have answered this call: like mushrooms, large global datasets and databases on soil physics, chemistry and ecology are sprouting up everywhere (e.g. Fine‐Root Ecology Database (Iversen et al., 2018), FunFun (Zanne et al., 2020), GlobalFungi (Větrovský et al., 2020), COntinuous SOil REspiration (Jian et al., 2020), Global distribution of earthworm diversity (Philips et al., 2019) etc.). It is now time to leverage synergies among these datasets to link the continuum of belowground processes to ecosystem functions (e.g. decomposition, nutrient cycling and soil respiration). Built on interdisciplinary and international collaborations, data synthesis that leads to a holistic understanding is one of the best ways of predicting the future of terrestrial ecosystems and for preserving ecosystem services under global change. In 2020, global interconnectedness was on display as we saw a pandemic sweep across the world in weeks. The pandemic allowed the Ecological Society of America (ESA) to enter a new digital era by holding a fully virtual conference. While technology cannot yet replicate all aspects of an in‐person conference, the virtual platform increased accessibility and reduced the climate impact of the annual conference. It also provided an opportunity for early‐career plant and microbial ecologists from five ESA Organized Oral Sessions and one Inspire Session to organize Ecology Underground, a two‐day program of live virtual talks and open discussions on integrative belowground ecology on 4 and 5 August 2020. Ecology Underground was sponsored by New Phytologist, the ESA Soil Ecology Section, the US Department of Energy, Biological and Environmental Research program and the Oak Ridge Institute for Science and Education (ORISE), and gathered 453 participants over two days. The online platform allowed for participation across the globe (37 countries were represented; Fig. 1) and was an opportunity to think creatively about how scientific discussions and global collaborations can take place, now and in the future. Open in a separate window Fig. 1 The online platform of Ecology Underground allowed for participation across the globe.

Extending the Heat Index to Quantify the Physiological Response to Future Warming: A Modelling Study

Backgrounds: The Heat Index is a widely used measure of apparent temperature that accounts for the effects of humidity using Steadman's model of human thermoregulation. Steadman's model, however, gives unphysical results in sufficiently hot and humid conditions, leading to an undefined Heat Index. In a business-as-usual climate scenario, an undefined Heat Index will become increasingly frequent, eventually occurring across a third of the planet at any given moment. Hence, an extension of the Heat Index to all conditions is needed, and the direct health impacts of an elevated Heat Index should be quantified. Methods: We extend the Heat Index to all conditions by allowing sweat to drip off the skin in very hot and humid conditions and, in severe conditions, allowing the body's core temperature to rise. The index is mapped onto measurable quantities, including the elevated core temperature in severe conditions and, in fatal conditions, the time it takes for the core to exceed a survivable temperature. The Heat Index is then calculated everywhere on Earth in a business-as-usual climate simulation up to the year 2300. Findings: By 2300, heat exhaustion, heat stroke, and even heat death are frequently the unavoidable consequences of being outdoors, even for healthy adults, over large swaths of Africa, Australia, India, South America, Eastern China, and the Midwestern and Eastern United States. Interpretation:During the preindustrial, all locations and times on Earth were survivable by a healthy adult with sufficient access to clothing, shade, and water. This will cease to be true with a continuation of business-as-usual warming. Funding Statement: This work was supported by the U.S. Department of Energy’s Atmospheric System Research program through the Office of Science’s Biological and Environmental Research program under Contract DE-AC02-05CH11231. Declaration of Interests: We declare no competing interests.

A Blueprint for an Inclusive, Global Deep-Sea Ocean Decade Field Program

The ocean plays a crucial role in the functioning of the Earth System and in the provision of vital goods and services. The United Nations (UN) declared 2021–2030 as the UN Decade of Ocean Science for Sustainable Development. The Roadmap for the Ocean Decade aims to achieve six critical societal outcomes (SOs) by 2030, through the pursuit of four objectives (Os). It specifically recognizes the scarcity of biological data for deep-sea biomes, and challenges the global scientific community to conduct research to advance understanding of deep-sea ecosystems to inform sustainable management. In this paper, we map four key scientific questions identified by the academic community to the Ocean Decade SOs: (i) What is the diversity of life in the deep ocean? (ii) How are populations and habitats connected? (iii) What is the role of living organisms in ecosystem function and service provision? and (iv) How do species, communities, and ecosystems respond to disturbance? We then consider the design of a global-scale program to address these questions by reviewing key drivers of ecological pattern and process. We recommend using the following criteria to stratify a global survey design: biogeographic region, depth, horizontal distance, substrate type, high and low climate hazard, fished/unfished, near/far from sources of pollution, licensed/protected from industry activities. We consider both spatial and temporal surveys, and emphasize new biological data collection that prioritizes southern and polar latitudes, deeper (> 2000 m) depths, and midwater environments. We provide guidance on observational, experimental, and monitoring needs for different benthic and pelagic ecosystems. We then review recent efforts to standardize biological data and specimen collection and archiving, making “sampling design to knowledge application” recommendations in the context of a new global program. We also review and comment on needs, and recommend actions, to develop capacity in deep-sea research; and the role of inclusivity - from accessing indigenous and local knowledge to the sharing of technologies - as part of such a global program. We discuss the concept of a new global deep-sea biological research program ‘Challenger 150,’ highlighting what it could deliver for the Ocean Decade and UN Sustainable Development Goal 14.

The UK biological-warfare program: dual-use contributions to the field of aerobiology

ABSTRACT Between 1940 and the late 1950s, the United Kingdom had a limited biological program to provide a retaliatory capability should UK forces be attacked using biological warfare (BW). Aspects of BW defense have been investigated from 1940 up to the present day. Techniques, processes, and equipment used within biological research programs are recognized to have dual-use applications; aerobiology is one such dual-use area. Research during these offensive and defensive eras of the UK BW research program has contributed to aerobiological science, leading to a number of positive changes in some areas, including laboratory safety; understanding of infection by the aerosol route; and survival, detection, and identification of airborne pathogens. This article will discuss the historical contributions made to aerobiology science, the global contemporary legislation that governs dual-use research, and a modern case study based upon this type of investigation. The article will contribute to our understanding of the dual-use aspects of a BW program.

UNESCO Chair of Developmental Biology: how an initiative that fostered careers in Developmental Biology impacted Brazilian Science.

The UNESCO Chair in Developmental Biology started in 1998, at the Institute of Biomedical Sciences of the Federal University of Rio de Janeiro, in Brazil. This Chair was a Brazilian-French initiative led by Professor Vivaldo Moura Neto and Professor Nicole Le Douarin, one of the most inspiring Developmental Biologists of the 20th and 21st centuries. The UNESCO Chair wanted to stimulate interest in Developmental Biology among Brazilian students and scientists by organizing annual international courses on Evolution and Developmental Biology at an advanced level. At the Federal University of Rio de Janeiro, the UNESCO Chair established an international laboratory for the permanent training of researchers and the development of research programs in Developmental Biology and related areas. Moreover, the program aimed at establishing an international network connecting Brazilian Universities and research centers in Latin America and Europe. The advanced hands-on courses, symposiums, and workshops promoted by this Chair inspired the careers of many young scientists. They generated new lines of research in Developmental Biology using a variety of animal models. This review does not intend to bring up all the historical events that marked the beginning of Developmental Biology in Brazil. Instead, it will be dedicated to highlighting one specific initiative that inspired a new generation of Developmental Biologists who established important research lines and contributed to the advance of this scientific field in Brazil.

Practical Recommendations for Supporting a Systems Biology Cyberinfrastructure

Projects in the life sciences continue to increase in complexity as they scale to answer deeper and more diverse questions. They employ technologies that generate increasingly large ‘omic’ datasets and research teams regularly include experts ranging from animal care technicians, veterinarians, human health clinicians, geneticists, immunologists, and biochemists to computer scientists, mathematical modelers, and data scientists, often located at different institutions. Providing the cyberinfrastructure support framework (IT, data management, communication, documentation, and aspects of project management related to these areas) for these projects requires a diverse set of technical tools and soft skills. These skills must be able to meet both the broad needs of data generators and consumers within the project and the needs of the larger scientific community. Here we describe recommendations for cyberinfrastructure support teams responsible for systems biology research programs. Recommendations are based on lessons learned while establishing and leading a complex, transdisciplinary, host-pathogen malaria systems biology consortium involving many institutions, a variety of disciplines, animal infectious disease models, and clinical studies. While some technical suggestions are included, the primary foci are situational and sociological challenges and tips for handling them.

Alternately Translated Product of Cx37 Fails to Arrest Growth in Rin Cells but Alters Cx37 Hemichannel Function when Co‐Expressed

Connexin proteins facilitate transmembrane and intercellular communication via channel formation (hemichannel) and intercellular docking of apposed hemichannels to form gap junction channels, respectively. Additionally, they play a role in determining growth phenotype (e.g., arrest, proliferation, death). Connexin 37 (Cx37), expressed in connexin‐deficient rat insulinoma (Rin) cells induces growth arrest or cell death in a manner dependent on the phosphorylation of specific carboxyl terminus (CT) residues. Notably, phosphorylation at serine 319 (S319) is both necessary and sufficient for growth arrest, and mimicking phosphorylation with aspartate substitution at either S275 or S321 is sufficient to induce cell death. 13 of the 21 members of the connexin gene family have a conserved methionine at position 213; in Cx43 mRNA, this methionine codon serves as an alternate translation start site that produces a CT‐spanning translation product. This 20kDa (20k) product interacts with Cx43, chaperoning its trafficking to the membrane. Here we test the hypotheses that 1) this conserved codon in Cx37 mRNA also serves as an alternate translation start site to produce a 13kDa product (13k) that, when expressed alone, regulates growth phenotype of Rin cells and 2) when co‐expressed with Cx37, regulates its channel function. To test these hypotheses, we expressed V5‐tagged 13k or one of two phosphomimetic mutants, 13k‐S321D and 13k‐S275D, in Rin cells or in Rin cells expressing Cx37. Despite a similar phosphorylation profile to Cx37, as determined by mass spectrometry, 13k did not arrest Rin cell growth and neither phosphomimetic mutant induced cell death nor growth arrest. In co‐expressing cells, immunoprecipitation (IP) of 13k failed to co‐IP full‐length Cx37, suggesting no direct interaction between these isoforms; however, 13k and the phosphomimetic mutants altered Cx37 hemichannel conductance and open probability properties, suggesting an indirect interaction of 13k isoforms with Cx37. In conclusion, these data suggest that while 13k and phosphomimetic mutants alone are insufficient to alter the growth phenotype of Rin cells toward growth arrest or death, they nevertheless lead to altered channel properties of full‐length Cx37. The findings herein will inform further research in understanding how connexins are regulated and, in turn, the role they play in regulating cell growth phenotypes.Support or Funding InformationR01 HL131712 | Undergraduate Biology Research Program | University Funds

Functional Connectivity of Prelimic Prefrontal Cortex and Rostral Ventromedial Medulla for Descending Pain Modulation

Chronic pain is a health condition that can seriously impact quality of life. To develop better treatments for chronic pain, a better understanding of the mechanisms behind pain perception is needed. Current models of descending pain modulation show the prelimbic prefrontal cortex (plPFC; area 32V) synapsing onto cells within the periaqueductal grey (PAG) which then synapses onto the rostral ventromedial medulla (RVM). The RVM contains ‘on’ and ‘off’ cells which respond to pain stimuli by respectively activating or inhibiting pain perception. We aim to functionally characterize a hypothesized direct projection from the plPFC to the RVM first described in 1997. Anterograde tracing was performed in the plPFC to determine the anatomical connectivity of the two regions. Similarly, we transfected the plPFC with hM4Dq DREADDs fused with mCherry under the control of CaMKIIa promoters to label glutamatergic Layer 5 projection neurons and determine functional connectivity of the purported circuit in animals with a spared nerve injury (SNI). These receptors are inert unless acted on by a designer drug, such as CNO. We used reverse microdialysis to locally deliver CNO into the RVM and activate DREADDs on neurons with direct projections from the plPFC while collecting released neurotransmitter and performing reflexive pain behaviors assays. This strategy allowed for avoidance of systemic/off target activation of plPFC neurons projecting to a different CNS region. Anatomical and microanalysis pilot data indicate a direct connection from plPFC to the RVM.Support or Funding InformationFunding provided by the University of Arizona Department of Medicinal Pharmacology, University of Arizona Undergraduate Biological Research Program, and the ASPET Summer Undergraduate Research Fellows Program.

Investigating Novel Turnover Mechanisms of Huntingtin in Yeast

Huntington’s disease is a devastating neurodegenerative disease which leads to symptoms of involuntary movements, memory loss, and ultimately death. The disease is characterized by a CAG repeat expansion mutation in the huntingtin (HTT) protein which leads to its aggregation inside the cytoplasm of striatum neurons. It is unknown whether these aggregates are directly toxic or if they reflect a cellular protection mechanism. Recently, endocytosis activity has been shown to reduce the toxicity, protein levels and propensity to aggregate of TDP‐43, a protein that forms potentially toxic aggregates in amyotrophic lateral sclerosis (ALS) patient motor‐neurons. Conversely, high expression of aggregation‐prone TDP‐43 can impair endocytosis function. Thus, there is a possibility that HTT aggregates, similar to TDP‐43 in ALS, will also inhibit endocytosis and be cleared by the endocytosis pathway. Using a Huntington’s disease yeast model, wild type and mutant HTT localize to the cytoplasm as well as the vacuole, an acidic organelle where proteins are trafficked by endocytosis for degradation. “WT” HTT with 25 CAG repeats is expressed diffusely throughout the cytoplasm while “pathological” HTT with 103 CAG repeats forms cytoplasmic aggregates, in addition to exhibiting diffuse cytoplasmic localization. Pathological HTT exhibits slight growth defects in vps34Δ and vps15Δ strains; these PI3K subunit genes are key to normal endocytic (and autophagic) function. Protein half‐life assays indicate that WT HTT has a slower turnover rate compared to the pathological HTT. Proteasome inhibition also slows WT HTT turnover but does not impact pathological HTT turnover rate. A genetic screen using the tet‐off regulatable promoter library will be conducted to determine for the first time what essential genes genetically interact with mutant HTT. Further microscopy and turnover assays will be conducted to determine if enhancement or suppression of endocytosis leads to clearance or accumulation of HTT in the vacuole respectively, and whether endocytosis activity represents a viable therapeutic target for Huntington’s disease.Support or Funding InformationThis project was funded by the University of Arizona Undergraduate Biology Research Program with funds from the Arnold and Mabel Beckman Foundation.