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Postbac Seminar Series: October 25, 2022

Series: Science Skills; Speaking

Oct 25, 2022

This event is recommended for: Postbacs.

Science isn't complete until the results have been shared with others, and talking about your results is one of the important ways of making them public. The Postbac Seminar Series provides a unique opportunity for two Postbacs each month to present their research to a diverse audience of their peers.  The atmosphere is relatively informal and non-threatening.  The series allows Postbacs who attend to learn about the different types of biomedical research being conducted at the NIH while meeting other postbacs.  Read more about the seminar series.

ONLINE MEETING INFORMATION:

The meeting information will be shared by email. If you have questions, please contact Lester Rodriguez Santos <lester.rodriguezsantos@nih.gov> and Omar El Merhebi <omar.elmerhebi@nih.gov>.

 

This month's presenters are:

Kaitlin Abrantes (NICHD)

Title: The Unknown “Potential” of the Mitochondrial Outer Membrane

Abstract: The primary role of the mitochondria is to supply the cell with energy as ATP through oxidative phosphorylation. Currently, it is understood that ATP synthesis is driven by the transmembrane potential across the mitochondrial inner membrane. In contrast, the mitochondrial outer membrane (MOM) has been assumed to be “leaky”, or having zero potential, due to the abundance of voltage-dependent anion channels (VDAC). VDAC is a transmembrane, β-barrel channel that resides in the MOM and is essential for metabolite transport between cytosol and mitochondria. Given its large pore size (1.4 nm), it is permeable to ions and metabolites <2 kDa. While VDAC does allow the diffusion of small ions and metabolites, research suggests that it is not completely passive. When reconstituted in a lipid membrane, VDAC exhibits voltage-dependent gating where the channel changes its permeability to Ca2+ ions and ATP/ADP in response to the applied potential. To study the physiological relevance of this voltage dependence, we are testing the conventional thinking regarding MOM by measuring the potential across MOM. Our approach is to measure the pH of the cytosol and intermembrane space (IMS) using a genetically encoded fluorescence probe called Sypher3s targeted to the cytosol and IMS, respectively. A pH difference would indicate potential across the MOM suggesting a voltage-dependent regulation of VDAC metabolite transport in cells. This would have greater implications for understanding VDAC’s role in the regulation of mitochondrial function and metabolism.

Bio: Kaitlin Abrantes graduated from Columbia University in 2022 with a major in Biomedical Engineering and a minor in East Asian Studies. She joined Dr. Sergey Bezrukov’s laboratory in the Section on Molecular Transport at the NICHD as a Post-baccalaureate IRTA Fellow in July 2022. Currently, she is investigating the role and regulation of VDAC, a mitochondrial outer membrane protein essential for metabolite transport between cytosol and mitochondria.

 

Liddy McCulla (NCI)

Title: Tumor-Derived Exosomal miRNAs Modulate Pericyte Pro-Metastatic Phenotypes

Abstract: Metastasis is responsible for the majority of breast cancer related deaths, and a crucial step in the metastatic cascade is the establishment of a pre-metastatic niche. A pre-metastatic niche is a pro-tumor microenvironment, formed in part by the activation of pericytes in response to tumor-derived secreted factors. Upon activation, pericytes acquire a proliferative, migratory, and matrix remodeling phenotype. We hypothesize that exposure to tumor-derived exosomal miRNAs induces pericyte activation in the pre-metastatic niche, given the ability of miRNAs to alter large gene expression networks in the setting of development of disease. Understanding the mechanism of phenotypic switching of pericytes in the context of pre-metastatic niche formation presents a new avenue through which to pursue potential therapeutic targets to prevent metastasis through alteration of perivascular cell plasticity. 

Bio: Elizabeth (Liddy) graduated from the University of Delaware in 2021 with a degree in Biological Sciences. As an undergraduate, she worked under Dr. Jia Song to study in influence of miRNAs on early embryonic development using the purple sea urchin as a model organism. During this time, Liddy became interested in the intersection of cancer and development, which motivated her to pursue a position in Dr. Meera Murgai’s lab at NCI. Outside of the lab, Liddy enjoys getting outside to hike and camp, going to concerts, and collecting cassette tapes.

 

Nina Westcott (NIAAA)

Title: Characterizing a novel high ketone ester diet

Abstract: Ketogenic diets, characterized by high fat and low carbohydrate content, have been shown to decrease alcohol withdrawal symptoms during abstinence periods in humans. Metabolism of alcohol renders acetate as a byproduct, which is subsequently metabolized into acetyl-CoA and used as an energetic intermediate in the TCA cycle. During the abstinence period after chronic alcohol use, the sudden decrease in circulating acetate is thought to contribute withdrawal symptoms. The ketogenic diet may alleviate these symptoms by providing an alternative metabolic pathway through ketosis. Although the ketogenic diet has been implicated as a beneficial technique in combating alcohol withdrawal symptoms, it also has drawbacks that may outweigh the benefits. These drawbacks include vitamin deficiencies and long-term effects on kidney function. Additionally, ketogenic diets are not sustainable, and many individuals give up after a short trial period. The drawbacks of ketogenic diets call for a new method of increasing blood ketone levels which eliminates the long-term effects of ketosis and allows for a more sustainable lifestyle. Ketone supplementation in addition to a regular diet has been shown to decrease alcohol drinking in rats. However, because of the bitter taste of the ketone ester, rats did not voluntarily consume it and the supplement was administered directly into the stomach using a gavage. Involuntary consumption is not favorable because of its anxiogenic effect in rodents. We aimed to develop a palatable rodent chow which is high in ketone ester but maintains similar nutrient composition as standard mouse chow. Our goal was to increase ketone levels in the blood through voluntary consumption and without inducing ketosis. After pilot studies testing various chow formulations, we determined mice would readily consumed chows that are peanut butter based with raspberry flavoring and with 33% ketone-ester content. We analyzed effects of these high ketone-ester diet (high KE diet) in comparison to a control chow of identical composition but without the ketone ester, and to standard NIH chow. We monitored the effect of the high KE diet on weight and circulating blood ketone and glucose levels over five weeks, after which we conducted a variety of behavioral tests to assess whether the high KE diet affected general behavior. The high KE diet was sustainable (i.e. readily consumed over the course of the study) in most mice and significantly increased blood ketone levels with no effect on glucose levels. Interestingly, we observed a significant drop in weight only in the high KE diet group despite similar consumption habits across groups. We found no remarkable effects of our diet on general behavior. Now that we know our diet is sustainable, increases blood KE levels, and does not have profound effects on behavior, we will begin to use this chow to address pre-clinical research questions related to substance abuse disorders.

Bio: Nina Graduated from Wake Forest University in 2021 with a major in Biology and minors in chemistry and psychology. She conducted undergraduate research at the Wake Forest Center for Addiction Research under Dr. Jeffrey Weiner where she studied neurocircuitry of addictive disorders. She decided to continue in the field and currently conducts research in addiction at the NIAAA under Dr. David Lovinger and Dr. Andrew Kesner. She is specifically interested in uncovering neurobiological mechanisms underlying addictive behaviors such as motivation and reward-seeking.