About

Matthew Gill, PhD, is an Associate Professor at the University of Minnesota Medical School. His research focuses on areas related to brain, nerve, and muscle health, with particular expertise in neuroscience and translational neuroscience. He is involved in the Gill Lab, which is part of the Institute for Translational Neuroscience, and his work includes studying neural dynamics, brain connectivity, and related experimental development and analysis. Dr. Gill's contributions include advancing understanding in neural circuit function and developing technological assistance for imaging and data analysis. His research supports the broader mission of the institute to create hope through discovery, emphasizing translational approaches to neurological health and disease.

Research topics

• Biology
• Genetics
• Cell biology
• Microbiology
• Endocrinology

Selected publications

• The Fourth Annual Symposium of the Midwest Aging Consortium

  The Journals of Gerontology Series A · 2024-11-01 · 1 citations

  articleOpen access

  The Midwest Aging Consortium (MAC) has emerged as a critical collaborative initiative aimed at advancing our understanding of aging and developing strategies to combat the rising prevalence of age-related diseases. Founded in 2019, MAC brings together researchers from various disciplines and institutions across the Midwestern United States to foster interdisciplinary geroscience research. This report summarizes the highlights of the Fourth Annual Symposium of MAC, which was held at Iowa State University in May 2023. The symposium featured presentations on a wide array of topics, including studies on slow-aging animals, cellular senescence and senotherapeutics, the role of the immune system in aging, metabolic changes in aging, neuronal health in aging, and biomarkers for measuring the aging process. Speakers shared findings from studies involving a variety of animals, ranging from commonly used species such as mice, rats, worms, yeast, and fruit flies, to less-common ones like naked mole-rats, painted turtles, and rotifers. MAC continues to emphasize the importance of supporting emerging researchers and fostering a collaborative environment, positioning itself as a leader in aging research. This symposium not only showcased the current state of aging biology research but also highlighted the consortium's role in training the next generation of scientists dedicated to improving the healthspan and well-being of the aging population.

  PublisherOA PDFDOI

• Feasibility and acceptability of multiple methods of recording injecting drug use episode data among people who inject drugs in Melbourne, Australia: a pilot evaluation study protocol

  BMJ Open · 2024-12-01

  articleOpen access

  INTRODUCTION: Opioid overdose and blood-borne virus transmission are key health risks for people who inject drugs. Existing study methods that record data on injecting drug risks mostly rely on retrospective self-reporting that, while valid, are limited to being broad and subject to recall bias. The In-The-Moment-Expanded (ITM-Ex) study will evaluate the feasibility and acceptability of multiple novel data collection methods to capture in situ drug injecting data. METHODS AND ANALYSIS: ITM-Ex will purposively recruit 50 participants from an existing longitudinal cohort (SuperMIX study) of people who inject drugs in Melbourne, Australia. Over a 4-week study period, participants will be asked to complete baseline/endline spirometry, continuously wear a heart rate monitoring device, complete short-form ecological momentary assessment (EMA) questionnaires for every injecting episode during the study period and return previously used needles/syringes for drug residue testing. These multiple data sources will be combined to conduct a comprehensive analysis of the physiological and risk characteristics of an estimated 800 individual injecting drug use episodes (if participants inject four times weekly). Finally, post-participation qualitative interviews will explore the acceptability of the data collection methods. ETHICS AND DISSEMINATION: Ethics approval for ITM-Ex was obtained from Alfred Hospital Ethics Committee (project number 368/22). Results will be disseminated via national and international scientific and public health conferences and peer-reviewed journal publications.Results from ITM-Ex may demonstrate vastly more complete and accurate methods of capturing data on injecting drug use risk and support future development and evaluation of devices to monitor and intervene during drug overdose. Further, ITM-Ex may demonstrate innovative methodologies to support myriad future public health research studies.

  PublisherOA PDFDOI

• The SR protein RSP-2 influences expression of the truncated insulin receptor DAF-2B in <i>Caenorhabditis elegans</i>

  G3 Genes Genomes Genetics · 2023 · 5 citations

  Senior authorCorresponding
  • Biology
  • Cell biology
  • Genetics

  The alternatively spliced daf-2b transcript in Caenorhabditis elegans encodes a truncated isoform of the nematode insulin receptor that retains the extracellular ligand binding domain but lacks the intracellular signaling domain and is therefore unable to transduce a signal. To identify factors that influence expression of daf-2b, we performed a targeted RNA interference screen of rsp genes, which encode splicing factors from the serine/arginine protein family. Loss of rsp-2 significantly increased the expression of a fluorescent daf-2b splicing reporter, as well as increasing expression of endogenous daf-2b transcripts. Correspondingly, rsp-2 mutants exhibited similar phenotypes to those previously observed with DAF-2B overexpression, namely suppression of pheromone-induced dauer formation, enhancement of dauer entry in insulin signaling mutants, inhibition of dauer recovery, and increased lifespan. However, the epistatic relationship between rsp-2 and daf-2b varied according to the experimental context. Increased dauer entry and delayed dauer exit of rsp-2 mutants in an insulin signaling mutant background were partially dependent on daf-2b. Conversely, suppression of pheromone-induced dauer formation and increased lifespan in rsp-2 mutants were independent of daf-2b. These data demonstrate that C. elegans RSP-2, an ortholog of human splicing factor protein SRSF5/SRp40, is involved in regulating the expression of the truncated DAF-2B isoform. However, we also find that RSP-2 can influence dauer formation and lifespan independently of DAF-2B.

  PublisherOA PDFDOI

• The C. elegans truncated insulin receptor DAF-2B regulates survival of L1 arrested larvae

  PLoS ONE · 2023-07-20 · 2 citations

  articleOpen accessSenior authorCorresponding

  We have previously characterized a truncated isoform of the C. elegans insulin-like receptor, DAF-2B, which retains the ligand binding domain but cannot transduce a signal due to the absence of the intracellular signaling domain. DAF-2B modifies insulin / insulin-like growth factor signaling-dependent processes, such as dauer formation and lifespan, by sequestering insulin-like peptides (ILP) and preventing signaling through full length DAF-2 receptors. Here we show that DAF-2B is also important for starvation resistance, as genetic loss of daf-2b reduces survival in arrested first stage larvae (L1). Under fed conditions, we observe daf-2b splicing capacity in both the intestine and the hypodermis, but in starved L1s this becomes predominantly hypodermal. Using a novel splicing reporter system, we observe an increase in the ratio of truncated to full length insulin receptor splicing capacity in starved L1 larvae compared with fed, that may indicate a decrease in whole body insulin responsiveness. Consistent with this, overexpression of DAF-2B from the hypodermis, but not the intestine, confers increased survival to L1 animals under starvation conditions. Our findings demonstrate that the truncated insulin receptor DAF-2B is involved in the response to L1 starvation and promotes survival when expressed from the hypodermis.

  PublisherOA PDFDOI

• Using <i>C. elegans</i> Genetics to Identify Regulators of μ‐Opioid Receptor Signaling

  The FASEB Journal · 2020-04-01

  article

  Opioids exert their analgesic effects by activating the μ‐opioid receptor (MOR), a G protein‐coupled receptor expressed in the nervous system. In addition to clinical pain relief, activation of MOR produces euphoria and leads to dependence. Despite significant process in understanding molecular mechanisms of MOR signaling, the regulatory mechanisms of MOR function are not fully understood. To better understand MOR regulation and to uncover genes influencing MOR signaling, we developed a genetic behavioral platform utilizing nematode C. elegans. Mammalian MOR was transgenically expressed in the nervous system of C. elegans endowing the resulting model (tgMOR) with opioid sensitivity. We validated tgMOR platform showing conservation of pharmacological properties and regulatory mechanisms of MOR mediated behavioral responsiveness. We then performed a large scale forward genetic screen isolating a population of mutants with altered opioid sensitivity. Integrating whole genome sequencing, CRISPR/Cas9 gene editing and transgenic rescue, we identified a set of candidate negative modulators of MOR signaling. One of these genes encoded an orphan GPCR, FRPR‐13. Our phylogenic and functional analysis revealed that mammalian ortholog of FRPR‐13 is GPR139. We found GPR139 to be extensively co‐expressed with MOR in the mammalian nervous system. Knockout of GPR139 in mice enhanced opioid analgesia and reward, but diminished withdrawal. These observations suggest the existence of an “anti‐opioid” system that regulates the extent of MOR signaling in vivo. Our findings further showcase the utility of C. elegans as a scalable platform for genetic discovery of novel GPCR signaling principles. Support or Funding Information This work was supported by an NIH Cutting Edge Basic Research Award (R21DA040406) to B.G. and K.A.M., DA036596 to K.A.M., and an NIH Center of Biomedical Research Excellence Grant (P20GM103638) to University of Kansas Genome Sequencing Core.

  PublisherDOI

• F Plasmids Are the Major Carriers of Antibiotic Resistance Genes in Human-Associated Commensal Escherichia coli

  mSphere · 2020 · 66 citations

  • Biology
  • Genetics
  • Microbiology

  , and likely to other related bacteria.

  PublisherDOI

• Healthy Worms

  Healthy ageing and longevity · 2020-01-01

  book-chapterCorresponding
  PublisherDOI

• List of Contributors

  Future Energy · 2020-01-01

  book-chapterOpen access
  PublisherDOI

• An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans

  eLife · 2020 · 29 citations

  Senior authorCorresponding
  • Biology
  • Cell biology
  • Genetics

  In the nematode C. elegans, insulin signaling regulates development and aging in response to the secretion of numerous insulin peptides. Here, we describe a novel, non-signaling isoform of the nematode insulin receptor (IR), DAF-2B, that modulates insulin signaling by sequestration of insulin peptides. DAF-2B arises via alternative splicing and retains the extracellular ligand binding domain but lacks the intracellular signaling domain. A daf-2b splicing reporter revealed active regulation of this transcript through development, particularly in the dauer larva, a diapause stage associated with longevity. CRISPR knock-in of mScarlet into the daf-2b genomic locus confirmed that DAF-2B is expressed in vivo and is likely secreted. Genetic studies indicate that DAF-2B influences dauer entry, dauer recovery and adult lifespan by altering insulin sensitivity according to the prevailing insulin milieu. Thus, in C. elegans alternative splicing at the daf-2 locus generates a truncated IR that fine-tunes insulin signaling in response to the environment.

  PublisherDOI

• Molecular dynamics simulations suggest stabilizing mutations in a de novo designed α/β protein

  Protein Engineering Design and Selection · 2019-07-01 · 15 citations

  articleOpen access1st author

  Designing functional proteins that can withstand extreme heat is beneficial for industrial and protein therapeutic applications. Thus, elucidating the atomic-level determinants of thermostability is a major interest for rational protein design. To that end, we compared the structure and dynamics of a set of previously designed, thermostable proteins based on the activation domain of human procarboxypeptidase A2 (AYEwt). The mutations in these designed proteins were intended to increase hydrophobic core packing and inter-secondary-structure interactions. To evaluate whether these design strategies were successfully deployed, we performed all-atom, explicit-solvent molecular dynamics (MD) simulations of AYEwt and three designed variants at both 25 and 100°C. Our MD simulations agreed with the relative experimental stabilities of the designs based on their secondary structure content, Cα root-mean-square deviation/fluctuation, and buried-residue solvent accessible surface area. Using a contact analysis, we found that the designs stabilize inter-secondary structure interactions and buried hydrophobic surface area, as intended. Based on our analysis, we designed three additional variants to test the role of helix stabilization, core packing, and a Phe → Met mutation on thermostability. We performed the additional MD simulations and analysis on these variants, and these data supported our predictions.

  PublisherOA PDFDOI

Recent grants

• Genetic analysis of a truncated insulin receptor.

  NIH · $2.0M · 2018–2024

• Endocannabinoid signaling and aging

  NIH · $1.9M · 2010–2016

• NIH Grant R21AG030192

  NIH · $435k · 2011

• The role of spin genes in autophagy and lifespan in C. elegans

  NIH · $532k · 2017–2019

• Genetic and Molecular Analysis of a Novel Insulin Regulatory Protein

  NIH · $524k · 2017–2020

Frequent coauthors

• Peter Clayton

  University of Manchester

  58 shared

• Vallo Tillmann

  Tartu University Hospital

  17 shared

• Stephen M. Shalet

  Manchester Academic Health Science Centre

  15 shared

• Manuel H. Aguiar‐Oliveira

  Universidade Federal de Sergipe

  13 shared

• Anita H. O. Souza

  Universidade Federal de Sergipe

  13 shared

• Gordon J. Lithgow

  Buck Institute for Research on Aging

  12 shared

• Marta Regina Silva Alcântara

  Universidade Federal de Sergipe

  11 shared

• Andrew Toogood

  Queen Elizabeth Hospital

  11 shared

Awards & honors

• Dr. James E. Rubin Medical Memorial Award
• Graduating Medical Student Research Award
• Veneziale-Steer Award
• Dr. Marvin and Hadassah Bacaner Research Awards
• Schmidt Steer Award