Lab Meeting

Leo Brueggeman

09/13/17

slides.com/leoo/lab-meeting

Systems Genetics of Neurodegeneration

Frauenchiemsee island, Chiemsee

Format

Isolation retreat

One week

25 young researchers (70% senior grad students, postdocs, residents, industry)

Represented countries: USA, Germany, Slovenia, France, UK, Australia, Sweden, Korea

Project focused

First 1/2 of week: 3-4 hrs of lectures per day + 4-5 hrs research time

Last 1/2 of week: Unscheduled group work w/ facilitator overview

2 Presentations + 1 'peer review' session of manuscript draft at end

Resources

Allen Brain Institute

- Mouse Brain Atlas (in situ hybridization, 20k genes)

- Spinal cord atlas (ISHybrid, 17k genes, mouse, young & adult)

- Developing mouse brain atlas (microarray)

- Mouse connectivity atlas (see projections of cells w/in the brain, specific cell lines)

- BrainSpan

- Allen human brain atlas

- Gliobastoma

- Aging, Dementia, and TBI (100 individuals, 80-100 yo)

- Allen cell types database (electrophysiology, morphology, and rnaseq, mouse only for now)

- Allen brain observatory (response of cortex to mice doing visual behaviors)

Allen Human Brain Atlas

Allen Mouse Brain Atlas

BxD (genenetwork.org)

Genotypes

Phenotypes

genenetwork.org

Group Project

Nathan Skene. Postdoc in Sten Linnarsson's lab at Karolinska Institute (Sweden). Wet & dry lab research focused on single cell, brain

Annika Sommer, graduating PhD student from University of Erlangen-Nuremberg. Wet lab research on Parkinson's disease

Zoe Hanss, 3rd year PhD student at Luxembourg Center for Systems Biomedicine. Wet lab research on Parkinson's disease

Sara Redensek, 3rd year PhD student at University of Ljubljana, Slovenia. Wet lab research on Parkinson's disease

The team

Wet lab scientists work on PD

Last talk was about DJ1, a mitochondrial 'PARK' gene

Agree project going to be on PD

Does PD have an enrichment of mitochondrial genes?

Source of dz genes	Association type
GWAS + familial genes	Causative
RNAseq from PD cases	Correlated

Mitomap: 1000+ genes involved w/ mitochondrial fxn

hypergeometric test => no enr

Risk factors (aging, addiction protective), prodromal phase

Maybe 'aging' mt genes enriched?

Broader: what organelles aff in PD - use subcellular location

Broader: what cell types aff in PD - use single cell data. Prodromal

Broader: what brain regions aff in PD - use Allen Inst data

Project Conception Map

Etiology of PD

	Cell type x1	...	Cell type xn
Gene y1 expr	5	0	0
...	2	2	2
Gene yn expr	0	1	4

Approach

Core idea:

	Cell type x1	...	Cell type xn
Gene y1 spec	5/5+0 = 1	0/0+5 = 0	0/0+5 = 0
...	2/6 = .33	2/6 = .33	2/6 = .33
Gene yn spec	0/4 = 0	1/4 = .25	3/4 = .75