Peter Freddolino, Ph.D.
The regulatory networks of bacteria play a key role in their information processing capabilities, coordinating and executing interactions with their environments. Quantitative, predictive models of these networks would be tremendously beneficial for facilitating the development of new antimicrobial therapies, enabling synthetic biology applications, and understanding bacterial evolution and ecology. Ultimately, the aim of my laboratory is to build a multiscale framework enabling modeling of bacterial regulatory networks at any level of detail, from atomistic to cellular. To this end, we develop and apply high-throughput experimental methods for measuring biomolecular interactions and cellular regulatory states in vivo, and for profiling the phenotypic consequences of regulatory changes. In tandem with these experimental approaches, we use molecular simulation and mathematical modeling to obtain high-resolution insight into the biomolecular interactions driving regulatory networks, and the systems-level effects of altering them.
More detailed information, and publication lists, are available on the Freddolino lab website.
Amanda Garner, Ph.D.
Amanda L. Garner is an Assistant Professor in the Department of Medicinal Chemistry, College of Pharmacy at the University of Michigan. She is also affiliated with the University of Michigan Program in Chemical Biology, Translational Oncology Program and Center for RNA Biomedicine. She received her Ph.D. in Chemistry in 2008 from the University of Pittsburgh working under the supervision of Professor Kazunori Koide in the areas of fluorescent chemosensors and solid-phase organic synthesis. She then completed NIH-funded postdoctoral studies in the laboratory of Professor Kim Janda at The Scripps Research Institute in La Jolla, California working in the area of chemical biology. Dr. Garner’s independent research integrates chemical biology, medicinal chemistry and molecular and cellular biology approaches for studying cap-dependent mRNA translation and microRNA-mediated gene regulation. In particular, her laboratory is focused on the development of conceptually new high-throughput screening assays for the identification of chemical probes. The anticipated outcome of these studies is the validation of mRNA translation-related targets for future drug discovery efforts and the betterment of human health.
Sundeep Kalantry, Ph.D.
The focus of Kalantry laboratory is to understand how X-chromosome inactivation occurs. X-inactivation equalizes X-linked gene expression between male and female mammals by transcriptionally inactivating one of the two X-chromosomes in females. X-inactivation is required for the viability of female cells and is a paradigm of epigenetic inheritance, given that within a shared nucleoplasm one X-chromosome of an identical pair becomes inactivated while the other remains active and that replicated copies of the inactive and active X-chromosomes faithfully maintain their transcriptional states across many cell division cycles. X-inactivation is controlled by long non-coding RNAs and chromatin/transcription regulators, both of which are a focus of our lab.
Markos Koutmos, Ph.D.
Markos Koutmos is an Assistant Professor in the Departments of Chemistry and Biophysics, with an affiliation with the graduate Program in Chemical Biology. Dr. Koutmos received his Diploma in Chemistry from the University of Athens, Greece, and obtained his Ph.D. in inorganic chemistry at the University of Michigan. He then trained in macromolecular crystallography in the laboratories of Drs. Martha Ludwig and Janet Smith before launching his independent career in the Department of Biochemistry and Molecular Biology at the Uniformed Services University of the Health Sciences.
Dr. Koutmos and his lab joined the University of Michigan in 2018. The Koutmos lab has a long-standing interest in understanding how the 3D structure and dynamics of proteins and RNAs drive their biological function. His lab combines chemistry, biophysics and biology approaches to build a foundation of basic knowledge for understanding the remarkable chemistries catalyzed by nature’s best enzymes, uncovering the roles of biomacromolecules in disease, and discovering new classes of therapeutic targets. The Koutmos lab is specifically interested in RNA modifications and RNA/protein interactions, in mitochondrial RNA biology and processing and in RNA structure and dynamics.
Jayakrishnan Nandakumar, Ph.D.
Nandakumar Lab utilizes a combination of biochemistry, structural biology, and cell biology to understand the molecular basis for end protection of human chromosome ends by the shelterin complex, and end replication by the ribonuclear protein enzyme telomerase. I started as an assistant professor at University of Michigan in Fall of 2013 and brought with myself extensive expertise in biochemistry, X-ray crystallography and human cell biology. Our group recently described how a mutation in the gene coding for TPP1 results in the telomerase deficiency disease, dyskeratosis congenita (Kocak et al). These studies were inspired by my postdoctoral efforts that discovered a surface in TPP1 called the TEL patch, which binds telomerase to recruit it to its site of action in the cell and facilitates telomere elongation. While our efforts on the TEL patch highlight our interest in end replication, my postdoctoral studies also interrogated in depth the role of TPP1, and its binding partner, POT1, in end protection. As part of my graduate studies I solved several crystal structures of RNA and DNA ligases bound to their ‘broken’ RNA/DNA substrates to illustrate how these two families of repair enzymes use distinct strategies for joining RNA versus DNA ends. Most recently, we have come across a novel form of gene regulation that involves an intragenic noncoding RNA, which differentially influences the fates of isoforms of a telomeric gene.
Melanie Ohi, Ph.D.
Melanie Ohi is fascinated by how proteins and nucleic acids organize into dynamic structures. Although our categorization of the number and assortment of protein interactions is increasing, we still lack knowledge about how collections of proteins are precisely assembled into macromolecular machines. Melanie’s research program is positioned to attack this formidable challenge.
Generating 3-D snapshots of protein complexes and molecular machines is invaluable for generating comprehensive mechanistic models. Yet, the dynamic nature of many protein assemblies makes them inherently difficult to study using traditional structural approaches, such as X-ray crystallography. A promising, and rapidly advancing technique for obtaining macromolecular structural information is cryo-electron microscopy (cryo-EM). By combining molecular EM with complementary structural, biochemical, biophysical and genetic methods, as well as, embracing a collaborative multi-team approach, we aim to address the molecular basis underling important biological processes even when no atomic resolution structures are available. Our research goal is to generate detailed molecular models that will provide biological insight into function.
Stephen C.J. Parker, Ph.D.
The Parker Lab at the University of Michigan is part of the Departments of Computational Medicine & Bioinformatics and Human Genetics, and is affiliated with the Genome Science Training Program at the Center for Statistical Genetics and the Center for RNA Biomedicine.
Our research group uses an integrative approach in the general fields of computational biology and functional genomics. The major goal of the lab is to generate mechanistic knowledge about how disease susceptibility is encoded in the non-coding portion of the genome, with a focus on type 2 diabetes.
Peter Todd, M.D., Ph.D.
Peter Todd, M.D., Ph.D. is the Bucky and Patti Harris professor of neurology in the University of Michigan Medical School and a staff physician at the Ann Arbor VA Medical Center. Dr. Todd graduated from the University of California, San Diego and obtained his medical and doctoral degrees at the University of Wisconsin. He completed a medical internship and residency in neurology at the Hospital of the University of Pennsylvania, and a research intensive fellowship in movement disorders and neurogenetics at the University of Michigan. Dr. Todd’s research targets the mechanisms by which RNA and RNA processing contribute to neurodegenerative disorders, with a specific interest in Fragile X-associated tremor ataxia syndrome (FXTAS). For his work on FXTAS pathogenesis, he received the 2014 Hagerman Prize from the National Fragile X Foundation. Dr. Todd serves as co-director of the Fragile X clinic at the University of Michigan where he sees adult patients with FXTAS, Fragile X Syndrome, and other Fragile X-associated Disorders.