Labs interested in BS/MS students

With BISP 199 availabilities


Primary Investigator Contact & Info

Projects Available Desired Qualifications

Scott Rifkin

Ecology, Behavior, and Evolution

sarifkin@ucsd.edu

 

General theme

The projects in the Rifkin lab generally focus on why individuals vary in some ways but not others. For example, if you look around you'll see tons of variation between different people, but very few people have third arms growing out of their chests. Some kinds of variation are allowed by how an organism develops while other kinds are excluded. We use techniques from developmental, evolutionary, and systems biology to study the processes that generate variation and their evolutionary consequences.

Project 1

Organisms respond to environmental conditions using sets of signaling pathways where receptors sense the environment and transmit this signal through a series of protein intermediates to the nucleus of a cell where new proteins are made. There can be variation between individuals at any step in this process from how they actually sense the environment to the fidelity with which they transmit the signal to how they interpret it to how they act on that interpretation. We are using nematode worms as a model system to dissect variation in how organisms make consequential decisions about their environments. During larval life, worms decide whether the conditions are good enough to continue to reproductive development or to put their development on pause and proceed to a spore-like state called dauer until things get better. This decision is influenced by the environment (obviously) but also by genetics and randomness. The project would involve setting up and using a microfluidic and microscopy system to manipulate this decision and monitor the developmental processes that underlie it at both the organismal and molecular levels. An ideal student for this project would be someone who is interested in evolutionary or developmental biology, who likes to tinker and get devices to work, and is excited about quantitative approaches to analyzing biology.

Project 2

When two species breed, their progeny often die before completing development. However, speciation is an ongoing process and so there are cases where two species haven't completely separated and so their offspring sometimes survive. We are studying the developmental biology of species incompatibility using the nematode genus Caenorhabditis as a model system. Hybrids between different species of worms often die during embryogenesis, but some species pairs can breed and produce viable and even fertile offspring. We are tagging histones with a fluorescent protein and then using confocal microscopy to visualize the development of these worms from very early in their life and measuring where things go wrong in inviable hybrids and how their development differs from hybrids that are successful. This project involves developmental biology, evolutionary biology, microscopy, and image analysis. This project requires a student who wants to learn how to work with worms and microscopy and who is excited about learning to analyze image data.

Project 3

Developmental processes are controlled by networks of interacting genes. Often these genes are transcription factors that regulate the activity of other genes. In Caenorhabditis elegans (the model roundworm), a cell becomes a gut cell if a short network of genes culminates in the expression of a particular transcription factor that then regulates hundreds of other genes to build the gut. Despite the fact that building a gut is important if an animal is to survive, this network originated within the evolutionary history of this genus. In other words, some species that are relatively closely related to C. elegans don't build their guts in this way. We are using this set of genes as a model system to study how a new developmental network can arise and evolve. This project would involve working and measuring proteins and also measuring gene expression at single molecule resolution in some non-model organisms. This project requires a student who has experience in wet lab molecular genetics and who wants to learn image analysis. Familiarity with evolutionary biology or developmental biology would also be useful. There will also be the opportunity to learn some techniques for measuring properties of protein-DNA interactions.

Project 4

Genes interact in complex networks. Various researchers have developed simplified, computational models of gene networks they can use for in silico (in the computer) experiments. We are using one such model to study the role of gene duplication in evolution of different cell types. A student who works on this project should already have programming experience (ideally in R, Matlab, or Python) and be interested in computational and evolutionary biology.

Project 5

Water bears (a.k.a. tardigrades) are an incredible group of organisms found all over the world (look them up online!) They are around 1/2 millimeter long, can weather extreme conditions, have survived trips to outer space, and can be revived after being frozen for 30 years! Very little is known about their developmental biology. This project would involve setting up a colony of water bears in the lab and starting to look at some basic developmental biology using microscopy. This project would require someone who is intrepid and independent, who is creative in troubleshooting and tinkering with conditions and protocols and who wants to explore a relatively understudied area of biology.

Stephanie Stanford

Clinical and Translational Research Institute

ststanford@ucsd.edu

We study protein tyrosine phosphatases, enzymes that play an important role in signal transduction and are critical for numerous cellular processes in health and disease. We have a project available to study how dysregulation of a protein tyrosine phosphatase contributes to cancer by causing anomalous signal transduction in tumor cells. The student will have the opportunity to gain exposure to cell biology, signal transduction, mouse models of cancer, and the basic biochemistry of protein tyrosine phosphatases.

Jack Bui

Medical Center Cancer Center

jbui@mail.ucsd.edu

 

  1. role of IFN in promoting cancer stem cells
  2. role of the cancercell in producing cytokines and initiating immune responses
  3. role of cell-cell fusion in cancer progression
  4. role of the cytokine IL-17D in antitumor and antiviral immunity
1. need to have cell culture experience

Stephen A. Spector

Division of Infectious Disease

saspector@ucsd.edu

 

The Dr. Stephen Spector laboratory has used molecular and Immunologic approaches to study host-virus interactions of human cytomegalovirus (CMV) and human immunodeficiency virus type-1 (HIV-1) with a particular emphasis developing novel approaches for the detection, treatment and eradication of persistent viruses. Current CMV related research is examining the role of CMV in endothelial cell inflammation and the development of cardiovascular diseases. The laboratory has been involved with HIV/AIDS research since the beginning of the epidemic. Current research examines HIV pathogenesis with a particular emphasis on host-virus interactions, and the associations of host genetic variants on HIV diseases progression and HIV-related diseases including CNS impairment in children and adults. The laboratory has also identified specific host genetic variants that are associated with mother-to-child transmission, HIV disease progression, and antiretroviral pharmacokinetics and adverse effects. The laboratory’s interest in the identification of host factors that affect HIV pathogenesis and neurocognitive impairment led to the novel finding that during permissive infection, HIV down-regulates autophagy to promote its own replication, and the induction of autophagy (using mTOR inhibitors as well as vitamin D3) inhibits HIV replication. Most recently, Dr. Spector’s laboratory has discovered that a Na+/K+-ATPase dependent mechanism of autophagy, termed autosis, has the potential to preferentially kill HIV persistently infected cells. This research has led to him to examine the association of host factors that control HIV replication with the goal of identifying novel strategies to eradicate HIV in order to cure persons infected with HIV.

GPA- 3.5 or higher

Prashant Mali

Bioengineering

pmali@ucsd.edu

 

We have several projects in the area of CRISPR-Cas based genome engineering that we are actively seeking motivated researchers for. Also here is the lab website for the students to further explore: http://mali.ucsd.edu

Frank L. Powell

Division of Physioolgy

fpowell@ucsd.edu

Projects Available

Our laboratory focuses on determining the genetic and molecular signals for physiological mechanism of neural plasticity and ventilatory acclimatization to chronic hypoxia. We study healthy people from sea level and adapted to high altitude in the Andes and Tibet, as well as patients with chronic lung disease and animal models, including transgenic mice. These studies are relevant to lung disease causing chronic sustained hypoxia and chronic mountain sickness, and sleep apnea that causes intermittent hypoxia. We are especially interested in mechanisms of susceptibility and tolerance to chronic hypoxia in microcircuits that control breathing in the central nervous system.

Our recent experiments study:

  • The effects of HIF-1α versus HIF-2α in neurons versus glia for plasticity in the CNS with chronic hypoxia.
  • The role of glia and inflammatory signals in acclimatization to chronic hypoxia.
  • Identifying therapeutic targets for manipulating neural plasticity in respiratory centers arising from chronic sustained versus intermittent hypoxia.
  • Genetic determinants of individual variation in the hypoxic ventilatory response, including adaptions in human populations native to high altitude.
  • Plasticity in the control of breathing in patients with chronic hypoxemia from lung disease.

We study the problem at multiple levels, translating from genetic and molecular mechanisms to the whole animal physiology. Experimental approaches include:

  • ventilatory responses, respiratory gas exchange and functional MRI in healthy humans during acclimatization to hypoxia at high altitude, and in patients with sleep apnea receiving various treatments,

  • measuring ventilatory responses, metabolism and respiratory muscle activity in conscious, freely moving, instrumented rats and transgenic mice,

  • temporally and spatially specific conditional gene deletion using loxP-Cre strategies in transgenic mice,

  • neurophysiological studies of chemoreceptor reflexes in anesthetized rats and mice

  • in vivo and confocal fluorescent imaging, immunohistochemistry and molecular biological measures of signals for neural plasticity.


For more information please see Frank Powell's UCSD Profiles page or the Division of Physiology website

Yury Miller

Department of Medicine

yumiller@ucsd.edu

The project will involve the structure-function characterization of the interaction between apoA-I binding protein (AIBP) and toll-like receptor-4 (TLR4). We have shown that AIBP regulates cholesterol trafficking in the plasma membrane and the integrity of lipid rafts, membrane microdomains that harbor activated TLR4. Cellular events following AIBP binding to TLR4 result in restraining TLR4-mediated inflammation. This mechanism is relevant to the pathogenesis of many chronic inflammatory processes, including atherosclerosis and neurodegeneration.

The student should have a strong background in biochemistry and molecular biology. S/he will learn and apply hands-on skills of molecular cloning, mutagenesis and protein-protein interactions.

Karl Willert

Cellular Molecular Medicine

kwillert@ucsd.edu

 

Blood cancers such as leukemia and lymphoma are currently treated by replacing a patient’s supply of blood stem cells through bone marrow transplant. If we could determine how to make blood stem cells in a dish instead, we would be able to circumvent the need for bone marrow donations, which are painful and difficult to come by. The Wnt signaling pathway is known to be important for maintenance of a lot of stem cell pools, including blood stem cells. We have identified that one Wnt in particular, Wnt9a, is important for making blood stem cells. Next, we are trying to determine which other molecules in the Wnt signaling cascade modulate this effect on blood stem cells. To do so, we use a combination of in vivo biology in zebrafish, and cell biology studies in mammalian cell lines.

Jim Golden

Molecular Biology

jwgolden@ucsd.edu

 

Genetic engineering of cyanobacterial natural product biosynthetic gene clusters to understand the biosynthetic pathways and to identify the specific compounds. We also have goals of expression of the natural products in heterologous cyanobacterial strains to obtain enough of the compounds for testing pharmacological activities.

Allen F. Ryan

Departments of Surgery/Otolaryngology and Neurosciences

aryan@ucsd.edu

 

My laboratory performs research in the field of otology, specializing in the characterization, treatment and prevention of hearing loss.  This includes studies on the molecular mechanisms of damage to sensory cells and neurons in the inner ear, with the aim of identify potential therapies.  We also use screen compound libraries using cochlear tissue from transgenic mice in which the inner ear sensory cells selectively express GFP.  We are performing a human genome-wide association study to identify genes associated with tinnitus and hearing loss.   In addition to our neuroscience research, we study the molecular substrates of pathogenesis and recovery in otitis media (ear infections), using gene knockout models and single-cell transcriptomics to identify inflammatory and innate immune defense genes that are active in this disorder.  Finally, we investigate novel methods for drug delivery to the middle and inner ears, including a newly discovered mechanism that actively transports particles across the intact tympanic membrane.

Alessandra Franco

Pediatrics

alfranco@ucsd.edu

 

Human Immunology laboratory with emphasis in T cell recognition and immunotherapy design. Current focus is the role of natural regulatory T cells that recognize the heavy constant region of immunoglobulins in down-regulating inflammation.

 

Techniques involved: flow cytometry, culture of primary cells, ELISA.

 Maike Sander

Sanford Consortium for Regenerative Medicine

masander@ucsd.edu

 

Diabetes is a complex disease characterized by the inability to control blood glucose levels. The hormone insulin is essential for blood glucose regulation, and insufficient insulin production underlies both type 1 and type 2 diabetes. Insulin is secreted into the bloodstream by pancreatic beta cells. In diabetes, beta cells fail to produce sufficient insulin due to either their destruction by the immune system (in type 1 diabetes) or an excessive demand for insulin exceeding beta cell functional capacity (in type 2 diabetes). Therefore, strategies to augment insulin production by improving beta cell function or increasing beta cell numbers have potential to restore blood glucose control in either type of diabetes.

To identify novel strategies for enhancing beta cell mass and function, we have sought to better understand how these processes normally occur during adaptation of beta cells to metabolic challenges. Prolonged changes in energy balance alter insulin demand and evoke coordinated adjustments to the number and function of beta cells. Thus, our studies have converged upon the roles of metabolic signaling in the adaptive processes of (1) beta cell proliferation and (2) enhancement of the insulin secretory response. Thus far, we have uncovered novel regulators of both beta cell replication as well as insulin secretion.

The Sander laboratory studies beta cell biology by employing genetic mouse models, animal physiology, genomics, and metabolomics. We have interrogated the roles of pathways of interest in beta cell adaptation to metabolic challenges using mouse models whose beta cells have been challenged through dietary, genetic, or pharmacological interventions. Future studies will assess the potential therapeutic value of modulating pathways of interest by investigating the effects in mouse models of diabetes. Furthermore, we will utilize genomic studies to determine the molecular mechanisms linking gene regulation to beta cell phenotypes (e.g. proliferation and insulin secretion). Through integration of our lab’s expertise in beta cell biology and genomics, we take a systems level approach to investigate the effect of gene perturbations on beta cell function.

Students will have the opportunity to play an important role in this exciting project. The student will work closely with scientists in the lab to generate mouse models of diabetes and monitor disease progression. Students will characterize various aspects of beta cell biology in these models, including determination of insulin secretion, monitoring beta cell proliferation, performing genomic studies, and assessing responsiveness to nutritional or signal transduction pathways. In parallel with mouse studies, culture models that mimic the diabetic environment will be utilized, enabling the application of cell culture tools such as CRISPR-Cas9 as well as validation in human beta cells. Through this experience, the student will learn techniques in animal physiology, endocrinology, molecular biology, and next generation sequencing. If interested, students will have the opportunity to interact with bioinformaticians to interrogate next generation sequencing data.

Previous laboratory and rodent handling experience is highly advantageous.