New paper on reducing resistance against CRISPR gene drive
May 7, 2018
A functioning gene drive mechanism could fundamentally change our strategies for the control of vector-borne diseases, such as malaria, dengue, and Zika. CRISPR homing gene drive promises such a mechanism, which could be used to rapidly spread genetic modifications among the mosquitoes that transmit these diseases. However, recent studies have shown that current drives would likely be unable to spread in insect populations due to the high rate at which resistance will evolve. In a our new study that was just published in PNAS, we provide the first experimental demonstration that guide RNA multiplexing can successfully reduce resistance rates, but also find that such an approach would still need to be combined with additional strategies to create drives that are efficient enough for use in wild populations.
Lab receives funding from Predator Free 2050
April 2, 2018
Predator Free 2050 Ltd is a non-profit organization committed to achieving an ambitious plan of the New Zealand government, in which they seek to eradicate the most-damaging introduced mammalian predators that seriously threaten their vulnerable native species. Our lab will join this effort by modeling gene drive strategies to inform New Zealanders as to the benefits and risks of this new genetic technology prior to any consideration of the development of such tools. In particular, we will extend our SLiM framework to enable the analysis of different CRISPR gene drive strategies for rodent control, focusing specifically on the feasibility, performance, risks, and possible confinement of proposed strategies under realistic assumptions of the population dynamics and expected evolutionary responses of the target populations.
March 22, 2018
Congratulations to postdoc Jackson Champer, who has just been awarded the prestigious Ruth L. Kirschstein fellowship (F32) from the NIH. This 3-year postdoctoral fellowship will provide funding for Jackson’s work on CRISPR gene drives. In particular, Jackson will study drive efficiency and resistance allele generation in diverse genetic backgrounds for different types of gene drives in insects. In addition to this experimental work, he will also pursue modeling of gene drive dynamics to study the ability of different drives to spread in geographically structured populations. We are very proud of you Jackson!
Editor’s choice award for our GENETICS paper
March 2, 2018
We are excited to announce that our paper on “Evolution of resistance against CRISPR gene drive” was chosen as one of the winners of the Editors’ Choice Awards for outstanding articles published in GENETICS in 2017! According to the journal: “The Editorial Board considered a diverse range of articles, finding many papers worthy of recognition. After much deliberation, they settled on one exceptional article for each of the three award categories: molecular genetics, quantitative genetics, and population and evolutionary genetics.” We feel very honored to be among the group of papers chosen for this award.
January 12, 2018
Congratulations to our undergraduate student Jingxian “Clara” Liu, who just won the prestigious Victoria Finerty Travel Award. The award, which honors the memory of Victoria Finnerty, has been established to support travel costs for undergraduates engaged in research to attend the Annual Drosophila Research Conference. This year’s fly meeting will be held Apr 11-15 in Philadelphia, PA. Clara will present her work on “Maximum likelihood estimation of sex-dependent fitness costs of a yellow mutant allele in Drosophila melanogaster“. Our postdoc Jackson Champer will also give a plenary talk at the meeting about his recent work on “A genome-wide association study to identify genetic targets affecting resistance allele formation in homing gene drives”. We are excited to see the Messer lab so well represented at the fly meeting. Congratulations to both Clara and Jackson!
Nathan presents beehive monitoring technology
November 16, 2017
Nathan Oakes and his partner Hailey Scofield, a doctoral student in the field of neurobiology and behavior, presented their new bee colony monitoring technology from their startup Combplex at the Innovation and Entrepreneurship Showcase. The event was held on November 14 in Washington, D.C. and hosted by the Association of Public and Land Grant Universities (APLU) and the Association of American Universities (AAU). Nathan and Hailey presented their research to several policymakers, including Rep. Lamar Smith, R-Texas, chairman of the House Science, Space and Technology Committee, and discussed the role of federal funding in helping startups like Combplex succeed. Just recently, the two won pitch competitions for Combplex at Cornell’s Entrepreneurship Kickoff in September and Entrepreneurship Summit. Way to go Nathan and Hailey!
Ivy League Undergraduate Research Symposium
November 4, 2017
Our undergraduate students Jingxian “Clara” Liu and Chen Liu, assisted by Anisha Luthra, will be presenting their exciting research on CRISPR gene drives at this year’s Ivy League Undergraduate Research Symposium, taking place on November 10-12 at the University of Pennsylvania. The Ivy League Undergraduate Research Symposium serves to promote cutting-edge, undergraduate research and facilitate a community of research-oriented individuals across the Ivy League. The primary goal of the symposium is to promote any and all outstanding undergraduate research, spanning across all academic disciplines. It’s a great honor to be invited to present at this prestigious symposium. Big congratulations to Clara, Chen, and Anisha!
“Ask me Anything” on PLoS Science Wednesday
August 30, 2017
Lab postdoc Jackson Champer appeared for a live 60 minute Q&A on redditscience, as part of the PLOS Science Wednesday on redditscience “Ask Me Anything” (AMA) series. Jackson did and amazing job answering questions from the public about our recent paper on gene drive resistance. For some time, this feature even made it to the top of the “most popular” list on reddit. The complete transcript of the Q&A is available here.
Lab receives NIH funding
August 23, 2017
The National Institute of Allergy and Infectious Diseases has awarded an R21 grant to the Messer lab for our experimental work on CRISPR gene drives, which we pursue in collaboration with the Clark lab at Cornell. The goal of the proposed work is to develop CRISPR gene drive constructs with reduced rate of resistance allele formation and to experimentally quantify the factors that are important to the evolution of resistance alleles in large cage populations of the model organism Drosophila melanogaster. The data generated by this project will also be key for informing our modeling work, in which we study the evolutionary dynamics of CRISPR gene drives in natural populations. We are very happy to see this level of support from the NIH. Congratulations to all members of the project, in particular postdoc Jackson Champer, who will spearhead the experimental work.
New paper on resistance against CRISPR gene drives
July 20, 2017
Gene drive systems provide a wide array of potential applications, including new strategies for the control of vector-borne diseases. However, resistance alleles can also be generated during this process, which may pose a major obstacle to the practical use of such gene drives. In our new study published today in PLoS Genetics, we developed two CRISPR/Cas9 gene drive constructs using different promoters and target sites in the model organism Drosophila melanogaster to study the mechanisms and rates by which such resistance alleles are generated. We observed that resistance alleles arise at high rates both in the germline and post-fertilization in the embryo. Additionally, conversion efficiency and resistance allele formation rates varied substantially among genetically diverse fly lines. The design of effective CRISPR gene drives will therefore require new approaches that reduce the formation of resistance alleles, particularly when applied to genetically diverse natural populations. This is the first experimental study of our lab and major congratulations go to postdoc Jackson Champer, who spearheaded this work and has been the driving force in setting up our experimental program. The paper is also accompanied by a perspective article by Jim Bull and Harmit Malik in the same issue and has already received extensive press coverage, including articles by The Economist, Science News, Gizmodo, and GEN. The paper was also chosen as a research highlight by Nature.
May 26, 2017
Congratulations to Andrew Marderstein for graduating with Honors in Biological Sciences from Cornell’s College of Agriculture and Life Sciences. Andrew has been a student in the lab since early 2016. In his honors thesis “Approximate Bayesian Computation for Studying Selective Sweep Signatures in Local Coalescence Trees”, Andrew explored whether we can distinguish hard and soft sweeps from the shape of the local coalescence tree at the sweep locus. For this purpose, he developed an Approximate Bayesian Computation (ABC) approach that can reliably distinguish these sweep types and infer their evolutionary parameters. In the Fall, Andrew will be starting as a graduate student in the Tri-Institutional PhD program for Computational Biology and Medicine from Cornell University, Weill Cornell Medical College, and Memorial Sloan Kettering Cancer Center. We congratulate Andrew on his impressive achievements and wish him the best in his future endeavors!
Commentary on gene drive resistance paper
March 1, 2017
In a commentary in the March issue of GENETICS, Floyd Reed discusses our recent paper Unckless et al. (2017), “Evolution of resistance against CRISPR/Cas9 gene drive,” which was published in the February issue of the journal. Reed highlights the issue of resistance against CRISPR gene drive approaches and proposes a possible path forward by synergistically combining the relative advantages of multiple gene drive systems. For example, Reed suggests that a CRISPR gene drive could be combined with an underdominance system, which cannot increase in frequency when rare but can proceed to fixation once a “threshold” allele frequency is surpassed. The CRISPR drive would then initially propel the drive, while the underdominance drive could continue to drive the system at higher frequencies.
New paper on gene drive resistance
February 2, 2017
CRISPR/Cas9 gene drive (CGD) promises a highly adaptable approach to controlling pests or disease vectors by spreading genetically engineered alleles throughout a species. In a new paper with co-authors Rob Unckless and Andy Clark we examine the likelihood that resistance to gene drive evolves prior to driver fixation, potentially limiting the ability of the driver to transform whole populations. The results shed light on possible strategies for engineering drivers with lower potential for resistance as well as the potential use of resistance as a mechanism for controlling CGD. We are excited to see that our paper was chosen as an issue highlight. And check out that stunning cover art depicting the attack of the 50-foot mosquito (unmistakeably inspired by the famous B-movie “Attack of the 50 Foot Women“) from artist friend Kent Smith, who we commissioned to illustrate our article. This work was also recently featured in a News story by Ewen Callaway in Nature.
SLiM 2 paper published in MBE
January 9, 2017
New paper on adaptive Neandertal introgression
November 29, 2016
The 2’-5’ oligoadenylate synthetase (OAS) locus encodes for three OAS enzymes (OAS1-3) involved in innate immune response. This region harbors high amounts of Neandertal ancestry in non-African populations. However, strong evidence of positive selection in the OAS region is still lacking. In a new paper that just came out in Genome Biology, we used a broad array of selection tests in concert with neutral coalescent simulations to clearly demonstrate a signal of adaptive introgression at the OAS locus. In collaboration with Luis Barreiro’s lab at the University of Montreal, we also characterized the functional consequences of the Neandertal haplotype in the transcriptional regulation of OAS genes at baseline and infected conditions. We found that cells from people with the Neandertal-like haplotype express lower levels of OAS3 upon infection, as well as distinct isoforms of OAS1 and OAS2. This haplotype is associated with functional consequences at the level of transcriptional regulation of innate immune responses. Notably, we suggest that the Neandertal-introgressed haplotype likely reintroduced an ancestral splice variant of OAS1 encoding a more active protein, suggesting that adaptive introgression occurred as a means to resurrect adaptive variation that had been lost outside Africa. Here is a link to a great article in The Scientist by Anna Azvolinsky, summarizing our work for a broader audience.
Can gene drives survive in the wild?
September 27, 2016
Monday, September 19, 2016
Genetic Engineering to Clash With Evolution
September 8, 2016
New paper on genetics of blue-winged and yellow-winged warblers
August 18, 2016
Seeing the upside in gene drives’ fatal flaw
July 15, 2016
Can population genetics adapt to rapid evolution?
July 10, 2016
New paper on adaptive Neandertal introgression
May 5, 2016
Detecting signatures of selective sweeps in dogs
January 11, 2016
New gene drive technology evokes hopes and fears
October 7, 2015
New paper on soft selective sweeps in Drosophila
February 26, 2015
SMBE Symposium: Population genomics of rapid adaptation
January 8, 2015
One of the most puzzling observations in evolutionary biology is that organisms can often adapt surprisingly quickly to environmental challenges. Classical examples of such rapid adaptations include the domestication of plants and animals and the evolution of pesticide or drug resistance. It is now becoming increasingly clear that the potential for rapid adaptation is a ubiquitous feature of evolution across a wide spectrum of systems, ranging from experimental evolution in microbes, to the progression of cancer cells in the human body, to the rapid responses of species under climate change. The growing number of systems where rapid adaptations are directly observable presents us with the fascinating opportunity to study evolution in real time and to make progress in understanding what limits the rate of evolution and determines its likely outcome. In this symposium, we will focus on (i) novel approaches to detect and study rapid adaptation using population genomic data, (ii) case studies of rapid adaptation in natural populations, and (iii) experimental studies of rapid adaptation in model systems. Although rapid adaptation has long been associated primarily with the evolution of polygenic traits that can adapt quickly by using standing genetic variation, we will also highlight recent work showing that adaptation at times can be rapid despite relying on de novo mutations.
Invited speakers: Graham Coop and Sasha Levy
Please do not hesitate to contact us with any questions. We hope to see you this summer!
Conundrum of Jumbled Mosquito Genomes
January 2, 2015
In this week’s issue of Science, Philipp Messer and Andy Clark wrote a perspective on two interesting papers that study the evolutionary genomics of mosquitos. The papers by Neafsey et al. and Fontaine et al. generate and analyze the genome sequences of 16 species of anopheline mosquitoes. Surprisingly, they reveal a complex pattern of evolution that defies the classic concept of a phylogenetic tree. Instead, the pattern of evolution seen in the An. gambiae species complex appears to rather resembles a network. These types of evolutionary networks are often referred to as reticulate evolution and are commonly observed in bacteria, where genetic exchange can be so pervasive that the concept of species becomes quite slippery. Even though reticulate evolution has also been seen in other species groups, the pattern in the gambiae complex of mosquitoes is so extreme that it, too, challenges any clear definition of species in this group. The two papers do a great job in advancing Anopheles genomics and providing baseline resources to answer many additional questions.
New paper on Soft sweeps and demography
August 6, 2014
When adaptation involves de novo mutations, the rate at which these mutations occur becomes very important for determining how adaptation proceeds. If beneficial mutations at a given locus arise frequently in the population, it is possible that several beneficial mutations originate independently in different individuals and sweep through the population at the same time, a phenomenon known as a soft selective sweep.
Soft selective sweeps are becoming an increasingly important model of adaptation as they have been observed in many case studies of rapid adaptation. Theory predicts that such soft sweeps should be observable in very large populations or when there are many mutations at a particular gene that can give rise to the adaptation, such as adaptive loss-of-function mutations or mutations that affect the expression level of a gene.
While the number of different mutations that give rise to a particular adaptation is typically fixed, the population size is not. In nature, population sizes often fluctuate by many orders of magnitude over timescales that overlap those during which adaptation occurs, for example during pathogen transmission or during population cycles over a season.
In our paper we develop a mathematical framework for predicting the likelihood of observing soft sweeps when population size changes over time. Using this framework, we show that in fluctuating populations soft selective sweeps that start during population booms can turn into hard sweeps when low frequency mutations drift out of the population during population busts. One striking consequences of this is that stronger adaptations are then more likely to produce soft sweeps than weaker adaptations, because strongly beneficial mutations can sweep to fixation between population crashes. Our results highlight the importance of understanding the recent demography of a species since it can be key for understanding the population genetic signatures that adaptation leaves in the data.
Evolution of drug resistance program at KITP
July 28, 2014
Philipp presenting at SMBE 2014
June 11, 2014
Credit to Alex Cagan (@ATJCagan) for this great sketch of my presentation.