Explore options for joint research and fellowship applications with the Metabolism Lab (NIH, Bethesda, USA)

Lina Schiffer, University of Birmingham

 

Aims

I am an early career postdoctoral research fellow at the Institute of Metabolism and Systems Research, University of Birmingham, UK.  I am currently developing a research project and identifying host laboratories for fellowship applications in 2020 (Sir Henry Wellcome Postdoctoral Fellowship, Marie Curie Global Fellowship). 

With the Bioscientifica Trust grant I will visit Dr Frank J Gonzalez at the Metabolism Laboratory, NHI National Cancer Institute, Centre for Cancer Research, Bethesda, USA with the overarching aim to establish collaborative links and explore opportunities for joint research to be conducted in the Metabolism Lab as part of a postdoctoral fellowship.

I believe that combining Dr Gonzalez expertise in liver metabolomics, nuclear receptor signalling and hepatic cytochromes P450 with my expertise in steroid biochemistry is a unique opportunity to develop a competitive, multifaceted project characterising novel pathways of liver steroid metabolism.

Specific aims:

1. Get an overview of knock-out and humanised mouse models available for hepatic cytochromes P450s and nuclear receptors
2. Visit the mass spectrometry platforms
3. Discuss my work with NIH researchers
4. Get insights into current projects in the Metabolism Lab and establish collaborations
5. Identify work packages of the fellowship to be conducted at Metabolism Lab

 

Evaluation

The specific aims 1-5 below had been identified for the visit at Dr Gonzalez Metabolism Lab at NIH and were achieved as described:

1. Get an overview of mouse models available

→ Dr Linda Gail Byrd, research geneticist overseeing the animal work, gave me an overview of mouse strains available, animal facilities and training in animal handling. We identified the strains relevant for joint research: CYP3A4-humanised mice and CYP3A4 global knock-out; PPARαglobal and liver-specific knock-out; HIF1αfl/fl and HIF2αfl/fl.

2. Visit the mass spectrometry platforms

→ I was given a tour of the laboratory by Kris Krausz, who manages the mass spectrometry platforms (two gas chromatography-mass spectrometry systems (Agilent), two UHPLC-tandem mass spectrometers (Waters, TQ-S and TQ-S micro) and two UHPLC-IMS-qTOF systems (Waters, Synapt)). Established metabolomics assays and sample preparation were discussed.

3. Discuss my work

→ I gave an open seminar about my current work with a 30-minute presentation and 30 minutes for discussion.

Additionally, I met with Dr Steven Soldin, who leads the mass spectrometry unit in the department of Laboratory Medicine in the Clinical Center, and his mass spectrometry team. We discussed implications of my current work for applications in the clinical lab.

4. Get insights into current projects in the Metabolism Lab

→ I had 1-to-1 meetings with 12 postdoctoral researchers in the lab. Discussions focused on the model systems available (nuclear receptor signaling; liver, intestinal and colon cancer; gut microbiome-intestine interaction).

5. Identify work packages of the fellowship to be conducted at Metabolism Lab

→ Dr Gonzalez and I discussed joint studies of alterations in steroid metabolism (my expertise) in metabolic disease and liver cancer (his expertise). We are now planning a project on alternative pathways of glucocorticoid clearance in the liver and its regulation by liver metabolic health and hypoxia.

 

Grant awarded: £1,130