I combine innovative ideas, large genomic data sets, and bioinformatics tools to create novel, interdisciplinary research programs.
The Microbiome, a totally fake movie trailer. But the science is 100% real. Microbes are important in all life and earth sciences. I study communities of microbes using a variety of molecular approaches. Read about some of my research below!
Produced by Mike Liguori (www.VisibleProofProductions.com) with technical consulting by Jessica Metcalf.
Microbial tools for forensics
Many basic hypotheses about the role of microbes in corpse decomposition that permeate both forensic science as well as pop culture (e.g. TV shows Bones, CSI) have not been tested with molecular tools. Rob Knight, David Carter, and I, along with a number of excellent collaborators, received funding from the National Institutes of Justice (NIJ 2011-DN-BX-K533, 2014-
R2-CX-K01, 2015-DN-BX-K016) to discover potential uses of microbes for forensic science.
Estimating the time since death, or postmortem interval (PMI), is important for criminal investigations because it can lead to the identification of the deceased and validate alibis. However, establishing PMI can be very challenging with few evidentiary tools available after the first after death. Our research demonstrates excellent potential of a microbial clock for estimating PMI. Please read about it in our most recent publication in the journal Science.
In a criminal investigation, establishing time of death is an essential but often difficult task for investigators. Thanks to innovations in the analysis of microbes, forensic teams may soon be able to use a "microbial clock" to recover this critical evidence in a much more accurate way than ever before.
Skin microbes also hold great potential for forensic science. People's skin is home to an individualized and generally stable microbial community that can be transferred to objects associated with a given person, such as computer keyboards, cell phones, and other commonly touched surfaces. We also found that humans transfer clouds of our microbes to the physical spaces we inhabit and that we come to share microbes with the humans and pets that we live with. We are currently studying how well skin microbes transfer to different common material types (glass, plastic, metal, ceramic and wood). We are also studying how long a person's skin microbial signature persists after death.
The ancestral gut microbiome
What is a healthy human gut microbiome? We are currently characterizing the human gut microbiome in cultures that have dramatically altered their microbial counterparts with intensive hygiene practices, widespread antibiotic use, high fat and protein diets, and extensive time spent indoors. We can try to understand the ancestral state of the human gut microbiome in two ways to do this – 1) study the microbiome of human populations living traditional lifestyles, particularly ones that haven’t been exposed to antibiotics and 2) by sampling ancient gut microbiomes in well preserved ancient human fecal material. I currently work on both of these types of projects. Through highly collaborative research projects, I study the gut microbiomes of people living traditional lifestyles today (e.g. hunter-gatherers). Additionally, I study gut microbiota preserved in ancient fecal material discovered in caves, Viking latrines, and naturally mummified human remains.
CONVERGENT EVOLUTION OF HOST MICROBIOMES
Do scavengers such as vultures and crows have similar gut microbes to help them digest their decomposing prey? In a Templeton Foundation funded project run by Valerie McKenzie, Rob Knight, and post-doc Se Jin Song, we are studying the co-evolution of vertebrate host microbiomes associated with convergent traits, such as extreme diets.
Check out our first paper here on the microbiomes of ant-eating mammals (myrmecophages).
LONGITUDINAL STUDY OF THE MICROBIOME OF APPENDICEAL CANCER PATIENTS
Appendix cancer is newly diagnosed in over 1,000 Americans a year. Recent research has revealed the presence, and potential role, of bacteria in tumor material of the appendiceal neoplasm Pseudomyxoma Peritonei (PMP) (1), which is a mucinous tumor type invades the peritoneal cavity. Gilbreath et al. (2013) showed that tumor/mucin microbiome was dominated by bacteria of the Phylum Proteobacteria such as Helicobacter. Helicobacter pylori has been implicated in other gastric cancers with antibiotic treatments effectively reducing tumor and improving survivorship in some cases. Similarly, a pilot study completed by the authors of this proposal demonstrated that antibiotic treatment increased survivorship for patients with the malignant form of PMP (Gilbreath et al. 2013, Semino-Mora et al. 2013), which is also associated with higher bacterial loads.
We hypothesize that tumor-promoting species are more prevalent in the fecal flora of PMP patients at the time of diagnosis, and these species could serve as both diagnostic and therapeutic targets. We will generate longitudinal gut microbiome data from the first 25 patients enrolled in clinical trial NCT02387203 and determine whether microbiome composition influences either carcinogenesis or post-surgical diarrheal illness, with the potential of markedly improving the quality of life of patients.
Extinctions of South American megafauna
One of my passions is the study of animals that became extinct during the late Pleistocene. What are their closest extant relatives? When did they became extinct? Were populations declining before extinction or did they became extinct suddenly? Is the timing of their extinction or population decline associated with changes in climate or human occupation of the region? A combination of radiocarbon data and DNA sequence data derived from teeth, bones, and other biological material provides clues to the answers of these questions. In collaboration with archaeologists and paleontologists, these data can be interpreted to help answer long-standing questions about the intriguing megafauna that no longer roam the earth. During my post-doc at ACAD, I worked on several projects in which we examined the late Pleistocene genetic diversity of large herbivores across a number of continents. In my focal study system of South American camelids, I uncovered previously undocumented extinction events in the Patagonia region of South America.
Conservation genetics of Colorado's greenback cutthroat trout
We clarified the taxonomy and diversity of cutthroat trout subspecies in the drainages of Colorado by using early museum collections (1857 – 1890 AD) of cutthroat trout. In my PhD research, I studied the population genetics and phylgenetics of modern cutthroat trout populations in Colorado, and demonstrated that early 20th century fish propagation and stocking activities had resulted in divergent lineages of cutthroat trout mixing across major drainage systems on both the Atlantic and Pacific slopes of the Continental Divide. The results demonstrated uncertainty about whether populations of the federally protected greenback cutthroat trout still existed (Metcalf et al. 2007). Subsequently, with funding and support from a wide range of federal and state agencies as well as Trout Unlimited, I successfully sequenced DNA recovered from 30 individuals of ~150 year old cutthroat trout specimens preserved in ethanol. The results of this research revealed recent extinctions, undescribed lineages, errors in taxonomy, and dramatic range changes induced by human movement of fish (Metcalf et al. 2012). We discovered that cutthroat trout lineages native to the Arkansas River and San Juan River, respectively, had become extinct since historic times. Our biggest surprise was the discovery of a single remaining population of greenback cutthroat trout (O. c. stomias) currently located outside of its native range in Bear Creek near Pikes Peak in the Arkansas River drainage. On August 8, 2014, in an effort spearheaded by the greenback cutthroat recovery team, our state fish was reintroduced to its native range.