About

Marco Archetti is an Associate Professor of Biology at Penn State University, affiliated with the Huck Institutes of the Life Sciences. His research focuses on evolutionary genetics, cancer dynamics, defective interfering viruses, and evolutionary game theory. He is involved with multiple research centers including the Center for Infectious Disease Dynamics, the Center for Cellular Dynamics, and the Molecular, Cellular, and Integrative Biosciences. His work has contributed to understanding the mechanisms of disease transmission, the development of innovative therapeutic strategies such as re-engineering cancerous tumors to self-destruct, and designing synthetic viruses to combat COVID-19. Archetti's research integrates evolutionary principles with biomedical applications, aiming to develop novel approaches to infectious diseases and cancer.

Research topics

• Biology
• Botany
• Virology
• Computational biology
• Ecology
• Biochemistry
• Chemistry
• Genetics

Selected publications

• A trans-amplifying mRNA vaccine with consensus spike elicits broadly cross-neutralizing antibody response against multiple SARS-CoV-2 variants

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-24

  preprint

  SARS-CoV-2 continues to evolve and evade vaccine immunity, necessitating vaccines that offer broad protection across variants. Conventional mRNA vaccines face cost and scalability challenges, prompting the exploration of alternative platforms like trans-amplifying (TA) mRNA that offer advantages in safety, manufacturability, and antigen dose optimization. Using consensus sequences of immunodominant antigens is a promising antigen design strategy for board cross-protection. Combining these two features, we designed and evaluated a TA mRNA vaccine encoding a consensus spike protein from SARS-CoV-2. Mice receiving the TA mRNA vaccine produced neutralizing antibody levels comparable to a conventional mRNA vaccine using 40 times less antigen mRNA. In hACE2 transgenic mice challenged with the Omicron BA.1 variant, the TA mRNA vaccine reduced lung viral titers by over 10-fold and induced broadly cross-neutralizing antibodies against multiple variants. These findings highlight the potential of TA mRNA vaccines with consensus antigen design to improve efficacy and adaptability against SARS-CoV-2 variants.

  PublisherDOI

• Defective but promising: evaluating the utility of currently available bioinformatic pipelines for detecting defective viral genomes in RNA-Seq data

  Journal of General Virology · 2025-11-17 · 1 citations

  articleOpen accessSenior author

  viral infections, and in theory can be detected from sequencing data. We explored the utility of the currently available bioinformatic programs ViReMa, DI-tector, DVGfinder, DG-Seq and VODKA2 for identifying junction points in plant virus high-throughput sequencing data, looking at whether the outputs from these bioinformatic tools generally agree and exploring the possibility of using these tools to help us understand whether DVGs are consistently generated and maintained in a specific virus-host combination. We conducted a meta-analysis of eight previously published RNA sequencing datasets utilizing all five programs and compared the degree of output overlap, the most common junctions present in each output and whether these junctions match previously reported junctions for that virus. Our results demonstrate a low degree of agreement regarding identified junctions between programs, including the most frequently identified one, although the most frequently identified junctions typically corresponded to large, disruptive deletions. We found preliminary support for our prevalence hypothesis, although we ultimately conclude that a more robust dataset generated expressly for testing this hypothesis will be required for a convincing answer. Finally, we suggest that when using bioinformatic programs to search for DVGs, it is best to run the same dataset through multiple programs and look at the overlap to inform decisions on downstream characterization.

  PublisherDOI

• Sociobiology meets oncology: unraveling altruistic cooperation in cancer cells and its implications

  Experimental & Molecular Medicine · 2025-01-07 · 5 citations

  reviewOpen accessCorresponding

  Altruism, an act of benefiting others at a cost to the self, challenges our understanding of evolution. This Perspective delves into the importance of altruism in cancer cells and its implications for therapy. Against the backdrop of existing knowledge on various social organisms found in nature, we explore the mechanisms underlying the manifestation of altruism within breast tumors, revealing a complex interplay of seemingly counteracting cancer signaling pathways and processes that orchestrate the delicate balance between cost and benefit underlying altruistic cooperation. We also discuss how evolutionary game theory, coupled with contemporary molecular tools, may shed light on understudied mechanisms governing the dynamics of altruistic cooperation in cancer cells. Finally, we discuss how molecular insights gleaned from these mechanistic dissections may fuel advancements in our comprehension of altruism among cancer cells, with implications across multiple disciplines, offering innovative prospects for therapeutic strategies, molecular discoveries, and evolutionary investigations.

  PublisherOA PDFDOI

• Female oviposition decisions are influenced by the microbial environment

  Journal of Evolutionary Biology · 2025-01-17 · 3 citations

  articleOpen access

  In ovipositing animals, egg placement decisions can be key determinants of offspring survival. One oviposition strategy reported across taxa is laying eggs in clusters. In some species, mothers provision eggs with diffusible defence compounds, such as antimicrobials, raising the possibility of public good benefits arising from egg clustering. Here we report that Drosophila melanogaster females frequently lay eggs in mixed-maternity clusters. We tested two hypotheses for potential drivers of this oviposition behaviour: (i) the microbial environment affects fecundity and egg placement in groups of females; (ii) eggs exhibit antimicrobial activity. The results partially supported the first hypothesis. Females reduced egg laying but did not alter egg clustering, on non-sterile substrates that had been naturally colonized with microbes from the environment. However, oviposition remained unaffected when the substrate community consisted of commensal (fly-associated) microbes. The second hypothesis was not supported. There was no evidence of antimicrobial activity, either in whole eggs or in soluble egg-surface material. In conclusion, while we found no behavioural or physiological evidence that egg clustering decisions are shaped by the opportunity to share antimicrobials, females are sensitive to their microbial environment and can adjust egg-laying rates accordingly.

  PublisherOA PDFDOI

• Female fruit flies use social cues to make egg-clustering decisions

  BMC Biology · 2025-10-14

  articleOpen access

  BACKGROUND: The ability to respond plastically to environmental variation is a key determinant of fitness. Females may use cues to strategically place their eggs, for example adjusting the number or location of eggs according to whether other females are present and driving the dynamics of local competition or cooperation. The expression of plasticity in egg-laying patterns within individual patches (i.e. in contact clusters or not) represents an additional, under-researched, and potentially important opportunity for fitness gains. Clustered eggs might benefit from increased protection or defence, and clustering could facilitate cooperative feeding. However, increased clustering is also expected to increase the risk of overexploitation through direct competition. These potential benefits and costs likely covary with the number of individuals present; hence, egg-clustering behaviour within resource patches should be socially responsive. We investigate this new topic using the fruit fly Drosophila melanogaster. RESULTS: Our mathematical model, parameterised by data, verified that females cluster their eggs non-randomly and increase clustering as group size increases. We also showed that as the density of adult females increased, females laid more eggs, laid them faster, and laid more eggs in clusters. Females also preferred to place eggs within existing clusters. Most egg clusters were of mixed maternity. CONCLUSIONS: Collectively, the results reveal that females express plasticity in egg clustering according to social environment cues and prefer to lay in clusters of mixed maternity, despite the potential for increased competition. These findings are consistent with egg-clustering plasticity being selected due to cooperative benefits.

  PublisherOA PDFDOI

• Trans amplifying mRNA vaccine expressing consensus spike elicits broad neutralization of SARS CoV 2 variants

  npj Vaccines · 2025-06-03 · 3 citations

  articleOpen access

  SARS-CoV-2 continues to evolve and evade vaccine immunity necessitating vaccines that offer broad protection across variants. Conventional mRNA vaccines face cost and scalability challenges, prompting the exploration of alternative platforms like trans-amplifying (TA) mRNA that offer advantages in safety, manufacturability, and antigen dose optimization. Using consensus sequence of immunodominant antigens is a promising antigen design strategy for board cross-protection. Combining these two features, we designed and evaluated a TA mRNA vaccine encoding a consensus spike protein from SARS-CoV-2. Mice receiving the TA mRNA vaccine produced neutralizing antibody levels comparable to a conventional mRNA vaccine using 40 times less antigen mRNA. In hACE2 transgenic mice challenged with the Omicron BA.1 variant, the TA mRNA vaccine reduced lung viral titers by over 10-fold and induced broadly cross-neutralizing antibodies against multiple variants. These findings highlight the potential of TA mRNA vaccines with consensus antigen design, to improve efficacy and adaptability against SARS-CoV-2 variants.

  PublisherOA PDFDOI

• Defective But Promising: Evaluating Bioinformatic Pipelines for Utility of Defective Interfering RNA Discovery in Plant Viral Infections

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-12

  preprintOpen accessSenior author

  Abstract We explored the utility of the currently available bioinformatics programs ViReMa, DI-tector, DVGfinder, DG-Seq, and VODKA2 for identifying junction points in plant virus high-throughput sequencing (HTS) data that could be tested downstream for antiviral capacity. Specifically, we looked at whether the outputs from these bioinformatic tools generally agree and whether the most frequently identified “defective viral genomes” (DVGs) from these programs are promising defective interfering RNA (DI) candidates for downstream validation. We also explored the possibility of these tools helping us address a larger research question of whether DI RNA are consistently generated and maintained in a specific virus-host combination when conditions are permissive for their replication and accumulation, our “DI prevalence” hypothesis. This was conducted by running eight previously published RNAseq datasets through all five programs and comparing degree of output overlap, most common junction point identified, and whether previously published DI junction points were found. Our results demonstrate a low degree of agreement regarding identified junction points between programs, promise regarding looking at the most commonly occurring junction for DI candidates, and support for our DI prevalence hypothesis. We conclude that bioinformatics workflows have a place in the toolbox of DI and DVG research, but they should not be used alone. We suggest the use of multiple programs on a dataset to better inform decisions regarding deletions to re-create and screen downstream and reiterate the importance of other avenues of evidence in DVG/DI characterization.

  PublisherOA PDFDOI

• Female fruit flies use social cues to make egg clustering decisions

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-05 · 2 citations

  preprintOpen access

  Abstract Background The ability to respond plastically to environmental variation is a key determinant of fitness. Females may use cues to strategically place their eggs, for example adjusting the number or location of eggs according to whether other females are present, driving the dynamics of local competition or cooperation. The expression of plasticity in egg laying patterns within individual patches, i.e., in contact clusters or not, represents an additional, under-researched and potentially important opportunity for fitness gains. Clustered eggs might benefit from increased protection or defence, and clustering could facilitate cooperative feeding. However, increased clustering is also expected to increase the risk of over-exploitation through direct competition. These potential benefits and costs likely covary with the number of individuals present, hence egg clustering behaviour within resource patches should be socially responsive. We investigate this new topic using the fruit fly Drosophila melanogaster . Results Our mathematical model, parameterised by data, verified that females cluster their eggs non-randomly, and increase clustering as group size increases. We also showed that, as the density of adult females increased, females laid more eggs, laid them faster, and laid more eggs in clusters. Females also preferred to place eggs within existing clusters. Most egg clusters were of mixed maternity. Conclusions Collectively, the results reveal that females actively express plasticity in egg clustering according to social environment cues and prefer to lay in clusters of mixed maternity, despite the potential for increased competition. These findings are consistent with egg clustering plasticity being selected due to public goods-related benefits.

  PublisherOA PDFDOI

• Altruism plasticity and byproduct-service exchange in the evolution of reciprocal cooperation in Escherichia coli

  2024-01-31

  preprintOpen access

  Explaining how cooperative individuals positively assort into a cohesive community is one of the greatest challenges for evolutionary biology. Here, we show that in antibiotic culture, many and even all of Escherichia coli bacteria cells will plastically mutate to be antibiotic resistant with the increase of antibiotic concentration and then altruistically protect antibiotic-sensitive individuals from the attack of antibiotics. A further experiment showed that antibiotic-sensitive E. coli strain could in turn help reduce the indole produced by the resistant strain;whistthis metabolic product is harmful to the growth of the antibiotic-resistant strain but benefits the antibiotic-sensitive strain by helping turn on the multi-drug exporter to discharge the antibiotic. A reciprocal cooperation can therefore evolve via a non-positive exchange between the metabolism byproduct indole of antibiotic-resistant cells and the indole-aborting service of antibiotic sensitive cells as unconscious help in nullifying indole side effect of antibiotic resistant strain.

  PublisherOA PDFDOI

• Tumor Heterogeneity Shapes Survival Dynamics in Drug-Treated Cells, Revealing Size-Drifting Subpopulations

  ACS Pharmacology & Translational Science · 2024-10-17

  articleOpen access

  The goal of this project was to demonstrate that subpopulations of cells in tumors can uniquely fluctuate in size in response to environmental conditions created during drug treatment, thereby acting as a dynamic “rheostat” to create a favorable tumor environment for growth. The cancer modeling used for these studies was subpopulations of melanoma cells existing in cultured and tumor systems that differed in aldehyde dehydrogenase (ALDH) activity. However, similar observations were found in other cancer types in addition to melanoma, making them applicable broadly across cancer. The approach was designed to show that either ALDHhigh and ALDHlow subpopulations rapidly epigenetically transition between stem-cell-like high into nonstem-like low production states to create an environment during drug treatment that would enable optimal cellular proliferation and tumor expansion to facilitate drug resistance. The controlled experiments showed proportional changes in each cell population to reach an evolutionarily stable equilibrium mediated by the needed levels of ALDH enzyme activity. Mechanistically, cell population size changes served to functionally move the aldehyde and the resulting reactive oxygen species (ROS) levels to those compatible with optimal cellular proliferation with population fluctuations dependent on the levels of drug induced tumor stress. This is the first report documenting fluctuations in the sizes of cell populations in tumors to cooperatively assist in drug resistance development.

  PublisherOA PDFDOI

Frequent coauthors

• Douglas W. Yu

  Chinese Academy of Sciences

  20 shared

• István Scheuring

  Centre for Ecological Research

  11 shared

• Shun Yao

  6 shared

• Helen Ougham

  Institute of Biological, Environmental and Rural Sciences

  5 shared

• Shantu Amin

  Pennsylvania State University

  5 shared

• Krishne Gowda

  Penn State Milton S. Hershey Medical Center

  5 shared

• Ines Pena‐Novas

  Pennsylvania State University

  4 shared

• Mikael Hartman

  National University Health System

  4 shared

Labs

• The Huck InstitutesPI