Tim works in Dr. Hanna Mikkola’s lab, researching how blood stem cells (the cells that give rise to all the many different kinds of blood cells) arise during early human development and are maintained throughout our lives. There are a huge number of factors that play into these processes, and understanding them is critical to developing treatments for blood disorders.
Tim became interested in a science career during high school when he visited a research laboratory studying infectious diseases. At UCLA, he started doing research as a freshman in Dr. Vatakis’s lab, studying neonatal HIV infections and treatment strategies. Eventually, he started working with blood stem cells (also known as hematopoietic stem cells), which led to his transitioning into Dr. Mikkola’s lab. After graduation Tim will be starting the NIH Postbac IRTA (Intramural Research Training Award) program before starting his graduate studies.
Gary Shmorgon is a post-graduate student who has successfully completed a Bachelor’s of Science in Biochemistry. He has been part Carla M. Koehler’s laboratory in the Chemistry and Biochemistry for over 4 years. Gary’s main research focus is in modeling mitochondrial defects of TOM70 and the implications this has towards cardiac function and ovarian development.
Defects in mitochondrial morphology and trafficking have been linked to diseases such as Charcot-Marie- Tooth disease (ataxia) and Parkinson’s disease. Often, these defects arise due to mutations in mitochondrial genes involved in the mitochondrial import pathway When Gary joined the lab, he was quickly interested in the zebrafish project. This project aims to create a model of translocase outer membrane protein 70 (TOM70) knockouts in zebrafish through the clustered regularly interspaced short palindromic repeats associated protein-9 nuclease (CRISPR/Cas9) technology. The CRISPR-Cas9 system utilizes a guide RNA to bind to the desired target DNA and cut that sequence using the Cas9 protein, which results in a genomic mutation. The goal is to obtain a frameshift mutation which results in the loss of protein activity. After many years of hard work, the TOM70 post-injections results indicate that the CRISPR-Cas9 system has been successful. The F 2 TOM70 generation, T2, has yielded two homozygous knockout zebrafish with a Δ2 insertion in the TOM70 coding region. In addition, immunoblotting of the TOM70 knockout zebrafish demonstrated that the protein is no longer present. Further characterization of these homozygous mutants has led the discovery of a sinus bradycardia phenotype and arrest in ovarian development specifically in the female homozygous mutant. In addition, increased levels of cytochrome and decreased levels of mitofusin 1 and 2 in both ovarian and cardiac tissue have led to the idea that the mitochondrial may be fragmented in these fish. Further histology and microscopy will be performed to better understand the morphology and overall phenotype.
Gary has matriculated into medical school and will be attending it during the upcoming cycle which begins in August. He would like to thank his mentor, Dr. Carla Koehler, in both her support and guidance during his time as a member of the Koehler lab. Gary would also like to thank his lab for dealing with him and providing him help along the way.
Project Title: Functional Characterization of Novel Microneme and Rhoptry Transporter Proteins inToxoplasma gondii
Andrew Lin is a fourth-year majoring in Microbiology, Immunology, and Molecular Genetics and minoring in Biomedical Research. He began as an undergraduate researcher with Dr. Bradley in the winter quarter of his freshman year. The Bradley lab studies the host-pathogen interactions of the apicomplexan parasite, Toxoplasma gondii. Andrew’s research focuses on novel proteins that localize to the microneme and rhoptry, two compartments involved in essential T. gondii invasion processes.
The Apicomplexa are a phylum of parasitic protozoa that includes Plasmodium falciparum, a parasite responsible for malaria, and Toxoplasma gondii, a widespread pathogen considered to be the leading cause of death attributed to foodborne illness. These parasites use a sophisticated strategy for infection, involving active invasion of their host cell, creation of a protective niche, and finally egress from the host cell. Effective apicomplexan invasion requires the polarized secretion of proteins from the micronemes, which are responsible for parasite attachment to the host cell. This is followed by secretion of proteins from the rhoptry, whose proteins are involved in both the hijacking of cellular machinery and the formation of a moving junction structure by which the parasite is able to pull itself into the host cell. While much is known about these released constituents of the microneme and rhoptry, very little is known about the transporter proteins in the delimiting membranes of these organelles. By studying these novel transporters, Andrew hopes to gain insight into the uncharacterized resident proteins of the microneme and rhoptry with the goal of ultimately contributing to the development of better therapies for these deadly parasites.
Andrew would like to thank Dr. Peter Bradley, all the members of the Bradley lab, and the URC-Sciences office for their assistance and guidance through his research, as well as for creating a great environment to develop as a scientist. Additionally, he would like to thank the Arnold and Mabel Beckman Foundation for their generous support and this invaluable research opportunity.