Genomics and Proteomicsfor Accurate, Fast, and Early

Detection of Disease

Ulf LandegrenRudbeck LaboratoryUppsala University

From a secret report by the CIA to the president of the United States

The level of research in Sweden was judged ”fair but not very high”

but Sweden was seen as leading in

”the development of new tools and new techniques in the biochemical and physichemical study of macromolecules and high molecular weight materials”

Sven Widmalm A Machine to Work in

Parallel DNA Sequencingand Personal Genome Sequencing

1000 genomes

23andMe

Plasma Protein Medium Abundance

1E-10

1E-09

1E-08

1E-07

1E-06

1E-05

0,0001

0,001

0,01

0,1

1

10

100

album

in IgGha

ptoglo

bin 2-

1 type

a-lipo

protein

(HDL

)b-l

ipopro

tein (L

DL) fibr

inoge

ntra

nsferr

ina1

-antitr

ypsin

a2-m

acrog

lobulin

IgAha

ptoglo

bbin 1

IgM

a1 ac

id glyc

oprot

einc3b

-comp

onen

tcer

ulopla

smin

hemo

pexin

a2 HS

-glyco

protein

inter- a

1-try

psin in

hibitor

a1 an

tichym

otryps

inGC

-glob

ulinC1

s inhib

itora1

b-gly

coprot

einIgD

Histidi

ne ric

h glyc

oprot

eina1

T gly

coprot

einpro

throm

bina1

M gly

coprot

einret

inol-b

inding

prote

ina3

glycop

rotein Ap

oC-III

a2 an

tiplasm

intra

nsferr

in Rfer

ritinmy

oglob

inlac

toferr

inb2

-micro

globb

ulinC-r

eactiv

e prot

einins

ulinPS

A (asy

mptom

atic)

comple

ment

C4 pr

ecurso

rCE

A (sm

oker, n

on ca

ncer)

prosta

tic aci

d pho

sphata

seTN

Fa (n

on inf

lamma

tory)

Protein

Log (

mg/m

L)

100

10

1

0.1

0.01

0.001

0.0001

1E-5

1E-6

1E-7

1E-8

1E-9

1E-10

?

1E-11

1E-12

1E-13

mg

/ml

Proteins in Plasma

Protein Analysis via DNA- Proximity Ligation Assays

Fredriksson Nature Biotechnol 20:473, 2002

“On Peculiar Disorder of the Cerebral Cortex”

Alois Alzheimer Auguste D

1997 1998 1999 2000

William Utermohlen’s self-portraits over the span of nearly four decades

1996 1996 19971967

0

20

40

60

80

100

120

2000 2025 2050(Years)

No

of

case

s in

Mil

lio

n

The current worldwide cost of dementia care is estimated at US$ 315.4 billion annually

Alzheimer’s Disease - Increasing Worldwide

22

27

32

37

42

1,0E-20 1,0E-18 1,0E-16 1,0E-14 1,0E-12

Aβ (mol)

Ct a

vera

ge

0,001

0,01

0,1

1

10

EL

ISA

(A45

0)

PLA

ELISA

0

Detection of Aβ Protofibrils; Homogenous PLA vs. ELISA

Masood Kamali Moghaddam, in progress

Protein Challenges

QuickTime och enTIFF (okomprimerat)-dekomprimerare

krävs för att kunna se bilden.

Analysis of biobank samples